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"FF00000001D5140E", "MaterialNumbers": [ "04939417190" ], "InstrumentReferences": [ { "ID": "2324", "BrandName": "cobas c 502" }, { "ID": "309", "BrandName": "cobas c 501" } ], "DisclaimerText": "Product information shown on this page contains elements of the officially released Method Sheet. If you require further information please refer to the full Method Sheet PDF under the given link, or contact your local Roche country representative." }, "Chapters": [ { "Name": "IntendedUse", "Value": "

Intended use

ONLINE DAT Benzodiazepines II (BNZ2) is an in vitro diagnostic test for the qualitative detection of benzodiazepines in human serum and plasma on Roche/Hitachi cobas c systems at a cutoff concentration of 200 ng/mL.

Benzodiazepines II provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC‑MS) or Liquid Chromatography coupled with Tandem Mass Spectrometry (LC‑MS/MS) is the preferred confirmatory method.

LREFKarch SB, ed. Drug Abuse Handbook. Boca Raton, FL: CRC Press LLC 1998.
,
LREFSalamone SJ, ed. Benzodiazepines and GHB: Detection and Pharmacology. Totowa, NJ: Humana Press 2001.
Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

", "Language": "en" }, { "Name": "TestPrinciple", "Value": "

Test principle

The assay is based on the kinetic interaction of microparticles in a solution (KIMS)

LREFBeck O, Lin Z, Brodin K, et al. The online screening technique for urinary benzodiazepines: comparison with EMIT, FPIA, and GC-MS. J Anal Toxicology 1997;21(7):554-557.
,
LREFArmbruster DA, Schwarzhoff RH, Hubster EC, et al. Enzyme immunoassay, kinetic microparticle immunoassay, radioimmunoassay, and fluorescence polarization immunoassay compared for drugs-of-abuse screening. Clin Chem 1993;39:2137-2146.
as measured by changes in light transmission. In the absence of sample drug, free antibody binds to drug-microparticle conjugates causing the formation of particle aggregates that are photometrically detected by turbidity measurements. As the aggregation reaction proceeds in the absence of sample drug, the absorbance increases.

When a serum sample contains the drug in question, this drug competes with the particle‑bound drug derivative for free antibody. Antibody bound to sample drug is no longer available to promote particle aggregation, and subsequent particle lattice formation is inhibited. The presence of sample drug diminishes the increasing absorbance in proportion to the concentration of drug in the sample. Sample drug content is determined relative to the value obtained for a known cutoff concentration of drug.

The presence of β‑glucuronidase enzyme enhances the Benzodiazepines II assay cross‑reactivity to some of the glucuronidated metabolites. Enzymatic cleavage makes the benzodiazepine part of the glucuronides more accessible for the antibody.

", "Language": "en" }, { "Name": "MeasuringRange", "Value": "", "Language": "en" }, { "Name": "ExpectedValues", "Value": "

Expected values

Qualitative assay

Results of this assay distinguish preliminary positive (≥ 200 ng/mL) from negative samples only. The amount of drug detected in a preliminary positive sample cannot be estimated.

", "Language": "en" }, { "Name": "LimitationInterference", "Value": "

Limitations - interference

Criterion: No cross‑over at initial values of samples of 100 ng/mL and 300 ng/mL (control levels).

See the \"Specific performance data\" section of this document for information on substances tested with this assay. There is the possibility that other substances and/or factors may interfere with the test and cause erroneous results (e.g., technical or procedural errors).

A preliminary positive result with this assay indicates the presence of benzodiazepines and/or their metabolites in serum. It does not reflect the degree of intoxication.

Icterus:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an I index of 60 for conjugated and unconjugated bilirubin (approximate conjugated and unconjugated bilirubin concentration: 1026 µmol/L or 60 mg/dL).

Hemolysis:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an H index of 1000 (approximate hemoglobin concentration: 622 µmol/L or 1000 mg/dL).

Lipemia (Intralipid):

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an L index of 2000. There is poor correlation between the L index (corresponds to turbidity) and triglycerides concentration.

Rheumatoid factors: No significant interference from rheumatoid factors up to a concentration of 1200 IU/mL.

Immunoglobulins: No significant interference from immunoglobulins up to a concentration of 16 g/L (simulated by human immunoglobulin A), up to a concentration of 70 g/L (simulated by human immunoglobulin G) and up to a concentration of 10 g/L (simulated by human immunoglobulin M).

Albumin: No significant interference from human serum albumin up to a concentration of 70 g/L.

In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.

LREFBakker AJ, Mücke M. Gammopathy interference in clinical chemistry assays: mechanisms, detection and prevention. Clin Chem Lab Med 2007;45(9):1240-1243.

For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.

ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on cobas c systems. The latest version of the carry‑over evasion list can be found with the NaOHD-SMS-SmpCln1+2-SCCS Method Sheets. For further instructions refer to the operator’s manual. cobas c 502 analyzer: All special wash programming necessary for avoiding carry‑over is available via the cobas link, manual input is required in certain cases.

Where required, special wash/carry‑over evasion programming must be implemented prior to reporting results with this test.

", "Language": "en" }, { "Name": "OrderInformation", "Value": "

OrderInformation (CC Reagents - cobas + Integra)

Order information

Analyzer(s) on which cobas c pack(s) can be used

04939417190

ONLINE DAT Benzodiazepines II (200 tests)

System‑ID 07 6997 5

cobas c 501/502

Materials required (but not provided):

03304671190

Preciset DAT Plus I calibrator CAL 5

Code 435

07978766190

Serum DAT Control Low (ACQ Partner Channel*)

07978740190

Serum DAT Control High (ACQ Partner Channel*)

04489357190

NaCl Diluent 9 % (50 mL)

System‑ID 07 6869 3

*Roche does not hold the product registration for Partner Channels. The legal manufacturer indicated on the kit is solely responsible for all of the design, legal, and regulatory aspects of the product.

", "Language": "en" }, { "Name": "SystemInformation", "Value": "

System information

For cobas c 501 analyzer:

BEQ2S: ACN 603 (Serum/plasma): for qualitative assay, 200 ng/mL

For cobas c 502 analyzer:

BEQ2S: ACN 8603 (Serum/plasma): for qualitative assay, 200 ng/mL

", "Language": "en" }, { "Name": "Handling", "Value": "

Reagent handling

Ready for use

Carefully invert reagent container several times prior to use to ensure that the reagent components are mixed.

", "Language": "en" }, { "Name": "TestDefinition", "Value": "

Application for serum and plasma

Deselect Automatic Rerun for these applications in the Utility menu, Application screen, Range tab.

cobas c 501/502 test definition

Qualitative

Assay type

2‑Point End

Reaction time / Assay points

10 / 16‑46

Wavelength (sub/main)

– /546 nm

Reaction direction

Increase

Unit

mAbs

Reagent pipetting

R1

90 µL

R2

40 µL

Sample volumes

Sample

200 ng/mL cutoff

Normal

4.5 µL

Decreased

4.5 µL

Increased

4.5 µL

", "Language": "en" }, { "Name": "StorageStability", "Value": "

Storage and stability

BNZ2

Shelf life at 2‑8 °C:

See expiration date on cobas c pack label

On‑board in use and refrigerated on the analyzer:

12 weeks

Do not freeze.

NaCl Diluent 9 %

Shelf life at 2‑8 °C:

See expiration date on cobas c pack label

On‑board in use and refrigerated on the analyzer:

12 weeks

", "Language": "en" }, { "Name": "Calibration", "Value": "

Calibration

Calibrators

Qualitative application

200 ng/mL cutoff assay

S1: Preciset DAT Plus I calibrator ‑ CAL 5, 1000 ng/mL with automatic pre‑dilution

The drug concentration of the calibrator has been verified by GC‑MS.

Calibration K Factor

Enter the K Factor as -1000 into the Calibration menu, Status screen, Calibration Result window.

Calibration mode

Qualitative application

Linear

Calibration frequency

Blank calibration
- after reagent lot change
- as required following quality control procedures

Calibration interval may be extended based on acceptable verification of calibration by the laboratory.

Traceability: This method has been standardized against a primary reference method (GC‑MS).

", "Language": "en" }, { "Name": "Limitations", "Value": "", "Language": "en" }, { "Name": "PerformanceData", "Value": "

Specific performance data

Representative performance data on the analyzers are given below. Results obtained in individual laboratories may differ.

", "Language": "en" }, { "Name": "Precision", "Value": "

Precision

A nordiazepam solution was added to 9 samples obtained from a human serum sample pool to achieve concentrations at approximately ‑100 %, ‑75 %, ‑50 %, ‑25 %, ±0 %, +25 %, +50 %, +75 %, and +100 % of the cutoff value. These samples were tested for precision. Following a CLSI (EP5‑A3) precision protocol, samples were tested in 2 replicates per run, 2 runs per day for 21 days, total n = 84. The following results were obtained on a cobas c 501 analyzer.

Drug

Concentration of Sample

Number of Determinations

Results
# Neg / # Pos

Nordiazepam

zero drug

84

84 Neg / 0 Pos

Nordiazepam

‑75 %

84

84 Neg / 0 Pos

Nordiazepam

‑50 %

84

84 Neg / 0 Pos

Nordiazepam

‑25 %

84

0 Neg / 84 Pos

Nordiazepam

cutoff

84

0 Neg / 84 Pos

Nordiazepam

+25 %

84

0 Neg / 84 Pos

Nordiazepam

+50 %

84

0 Neg / 84 Pos

Nordiazepam

+75 %

83

0 Neg / 83 Pos

Nordiazepam

+100 %

84

0 Neg / 84 Pos

", "Language": "en" }, { "Name": "MethodComparison", "Value": "", "Language": "en" }, { "Name": "Summary", "Value": "

Summary

The benzodiazepines constitute a class of versatile and widely prescribed central nervous system (CNS) depressant drugs with medically useful anxiolytic, sedative, hypnotic, muscle relaxant, and anticonvulsant activities.

LREFKarch SB, ed. Drug Abuse Handbook. Boca Raton, FL: CRC Press LLC 1998.
,
LREFSalamone SJ, ed. Benzodiazepines and GHB: Detection and Pharmacology. Totowa, NJ: Humana Press 2001.
,
LREFHardman JG, Limbird LE, Gilman A, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw Hill Pub Co. 2001.
,
LREFBaselt RC. Disposition of Toxic Drugs and Chemicals in Man. 7th ed. Foster City, CA: Biomedical Publications 2004.
,
LREFLaurijssens BE, Greenblatt DJ. Pharmacokinetic-pharmacodynamic relationships for benzodiazepines. Clin Pharmacokinet 1996;30:52-76.
The absorption rates, distribution, metabolism, and elimination rates differ significantly among the benzodiazepine derivatives. The quantitative differences in their potencies, pharmacodynamic spectra, and pharmacokinetic properties have led to various therapeutic applications. Clinical distinction of short‑acting versus long‑acting benzodiazepines have been observed in their efficacy, side effect, withdrawal, and dependence potential.
LREFHardman JG, Limbird LE, Gilman A, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw Hill Pub Co. 2001.
,
LREFHallfors DD, Saxe L. The dependence potential of short half-life benzodiazepines: a meta-analysis. Am J Public Health 1993;83:1300-1304.
,
LREFChouinard G. Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound. J Clin Psychiatry 2004:65(5);7-12.
The extensive and efficacious therapeutic use of the benzodiazepines over the last several decades has inadvertently led to their misuse. Benzodiazepine overdoses are frequently associated with co‑administration of drugs of other classes.
LREFAbernethy DR, Greenblatt DJ, Ochs HR, et al. Benzodiazepine drug-drug interactions commonly occurring in clinical practice. Curr Med Res Opin 1984;8:80-93.
,
LREFTanaka E. Toxicological interactions between alcohol and benzodiazepines. J Toxicol Clin Toxicol 2002;40:69-75.
Acute or chronic alcohol ingestion and benzodiazepines co‑administered may lead to various significant toxicological interactions. The net effect may be influenced by internal, external, and pharmacokinetic factors. Abuse patterns may involve relatively low benzodiazepine doses, as well as high‑dose overuse.

Following ingestion, the benzodiazepines of the 1,4‑substituted class (including the triazolobenzodiazepine derivatives) are absorbed, metabolized, and excreted in the urine at different rates as a variety of structurally related metabolites. Metabolite diversity reflects the different physiochemical properties and metabolic pathways of the individual drugs. Overall metabolic similarities include removal of substituents from the β ring of the 1,4‑substituted benzodiazepines, α‑hydroxylation of the triazolobenzodiazepines, demethylation, hydroxylation of the three‑position carbon of the β ring, and conjugation of hydroxylated metabolites followed by urinary excretion predominantly as glucuronides.

LREFKarch SB, ed. Drug Abuse Handbook. Boca Raton, FL: CRC Press LLC 1998.
,
LREFSalamone SJ, ed. Benzodiazepines and GHB: Detection and Pharmacology. Totowa, NJ: Humana Press 2001.
,
LREFHardman JG, Limbird LE, Gilman A, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw Hill Pub Co. 2001.
,
LREFBaselt RC. Disposition of Toxic Drugs and Chemicals in Man. 7th ed. Foster City, CA: Biomedical Publications 2004.
,
LREFLaurijssens BE, Greenblatt DJ. Pharmacokinetic-pharmacodynamic relationships for benzodiazepines. Clin Pharmacokinet 1996;30:52-76.
The enzymatic hydrolysis of glucuronidated benzodiazepines can increase their cross‑reactivities to benzodiazepine immunoassays.
LREFDou C, Bournique JS, Zinda MK, et al. Comparison of the Rates of Hydrolysis of Lorazepam-Glucuronide, Oxazepam-Glucuronide and Temazepam-Glucuronide Catalyzed by E. Coli β-D-Glucuronidase Using the OnLine Benzodiazepine Screening Immunoassay on the Roche/Hitachi 917 Analyzer. J of Forensic Science 2001;46(2):335-340.
,
LREFBeck O, Lin Z, Brodin K, et al. The online screening technique for urinary benzodiazepines: comparison with EMIT, FPIA, and GC-MS. J Anal Toxicology 1997;21(7):554-557.
,
LREFSalamone SJ, Honasoge S, Brenner C, et al. Flunitrazepam excretion patterns using the Abuscreen OnTrak and OnLine immunoassays: comparison with GC-MS. J Anal Toxicol 1997;21:341-345.
,
LREFKlette KL, Wiegand RF, Horn CK, et al. Urine benzodiazepine screening using Roche Online KIMS immunoassay with beta-glucuronidase hydrolysis and confirmation by gas chromatography-mass spectrometry. J Anal Toxicol 2005;29:193-200.
,
LREFValentine JL, Middleton R, Sparks C. Identification of urinary benzodiazepines and their metabolites: comparison of automated HPLC and GC-MS after immunoassay screening of clinical specimens. J Anal Toxicol 1996;20(6):416-424.

", "Language": "en" }, { "Name": "Reagents", "Value": "

Reagents - working solutions

R1

Benzodiazepines antibody (sheep polyclonal); buffer; β‑glucuronidase enzyme; bovine serum albumin (BSA); 0.09 % sodium azide

R2

Conjugated benzodiazepine derivative microparticles; buffer; 0.09 % sodium azide

R1 is in position A and R2 is in position B.

", "Language": "en" }, { "Name": "PrecautionsWarnings", "Value": "

Precautions and warnings

For in vitro diagnostic use for health care professionals. Exercise the normal precautions required for handling all laboratory reagents.

Infectious or microbial waste:
Warning: handle waste as potentially biohazardous material. Dispose of waste according to accepted laboratory instructions and procedures.

Environmental hazards:
Apply all relevant local disposal regulations to determine the safe disposal.

Safety data sheet available for professional user on request.

", "Language": "en" }, { "Name": "Caution", "Value": "", "Language": "en" }, { "Name": "QualityControl", "Value": "

Quality control

For quality control, use control materials as listed in the \"Order information\" section.

In addition, other suitable control material can be used.

Drug concentrations of the high and low controls have been verified by GC‑MS.

The control intervals and limits should be adapted to each laboratory’s individual requirements. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.

Follow the applicable government regulations and local guidelines for quality control.

", "Language": "en" }, { "Name": "SpecimenPreparation", "Value": "

Specimen collection and preparation

For specimen collection and preparation only use suitable tubes or collection containers.

Only the specimens listed below were tested and found acceptable.
Serum: Serum tubes with and without separating gel.
Plasma: K2‑ or K3‑EDTA, lithium heparin.

Stability:

5 days capped at 15‑25 °C

14 days capped at 2‑8 °C

6 months capped at -20 °C

The sample types listed were tested with a selection of sample collection tubes that were commercially available at the time of testing, i.e. not all available tubes of all manufacturers were tested. Sample collection systems from various manufacturers may contain differing materials which could affect the test results in some cases. When processing samples in primary tubes (sample collection systems), follow the instructions of the tube manufacturer.

Centrifuge samples containing precipitates before performing the assay.

See the limitations and interferences section for details about possible sample interferences.

Specimens can be repeatedly frozen and thawed up to 3 times.

Invert thawed specimens several times prior to testing.

CAUTION: Specimen dilutions should only be used to interpret results of Calc.? and Samp.? alarms, or when estimating concentration in preparation for GC‑MS or LC‑MS/MS. Dilution results are not intended for patient values. Dilution procedures, when used, should be validated.

", "Language": "en" } ] } }, { "ProductSpecVariant": { "MetaData": { "DocumentMaterialNumber": "0104939417190c501", "ProductName": "BNZ2", "ProductLongName": "ONLINE DAT Benzodiazepines II", "Language": "en", "DocumentVersion": "9", "DocumentObjectID": "FF000000045EB00E", "DocumentOriginID": "FF0000000058590E", "MaterialNumbers": [ "04939417190" ], "InstrumentReferences": [ { "ID": "308", "BrandName": "cobas c 311" }, { "ID": "2324", "BrandName": "cobas c 502" }, { "ID": "309", "BrandName": "cobas c 501" } ], "DisclaimerText": "Product information shown on this page contains elements of the officially released Method Sheet. If you require further information please refer to the full Method Sheet PDF under the given link, or contact your local Roche country representative." }, "Chapters": [ { "Name": "IntendedUse", "Value": "

Intended use

Benzodiazepines II (BNZ2) is an in vitro diagnostic test for the qualitative and semiquantitative detection of benzodiazepines in human urine on Roche/Hitachi cobas c systems at cutoff concentrations of 100 ng/mL, 200 ng/mL, and 300 ng/mL.

Semiquantitative test results may be obtained that permit laboratories to assess assay performance as part of a quality control program.

Benzodiazepines II provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC‑MS) or Liquid Chromatography coupled with Tandem Mass Spectrometry (LC‑MS/MS) is the preferred confirmatory method.

LREFKarch SB, ed. Drug Abuse Handbook. Boca Raton, FL: CRC Press LLC 1998.
,
LREFSalamone SJ, ed. Benzodiazepines and GHB: Detection and Pharmacology. Totowa, NJ: Humana Press 2001.
Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

", "Language": "en" }, { "Name": "TestPrinciple", "Value": "

Test principle

The assay is based on the kinetic interaction of microparticles in a solution (KIMS)

LREFBeck O, Lin Z, Brodin K, et al. The online screening technique for urinary benzodiazepines: comparison with EMIT, FPIA, and GC-MS. J Anal Toxicology 1997;21(7):554-557.
,
LREFArmbruster DA, Schwarzhoff RH, Hubster EC, et al. Enzyme immunoassay, kinetic microparticle immunoassay, radioimmunoassay, and fluorescence polarization immunoassay compared for drugs-of-abuse screening. Clin Chem 1993;39:2137-2146.
as measured by changes in light transmission. In the absence of sample drug, free antibody binds to drug-microparticle conjugates causing the formation of particle aggregates that are photometrically detected by turbidity measurements. As the aggregation reaction proceeds in the absence of sample drug, the absorbance increases.

When a urine sample contains the drug in question, this drug competes with the particle‑bound drug derivative for free antibody. Antibody bound to sample drug is no longer available to promote particle aggregation, and subsequent particle lattice formation is inhibited. The presence of sample drug diminishes the increasing absorbance in proportion to the concentration of drug in the sample. Sample drug content is determined relative to the value obtained for a known cutoff concentration of drug.

The presence of β‑glucuronidase enzyme enhances the Benzodiazepines II assay cross‑reactivity to some of the glucuronidated metabolites. Enzymatic cleavage makes the benzodiazepine part of the glucuronides more accessible for the antibody.

", "Language": "en" }, { "Name": "MeasuringRange", "Value": "", "Language": "en" }, { "Name": "ExpectedValues", "Value": "

Expected values

Qualitative assay

Results of this assay distinguish preliminary positive (≥ 100 ng/mL, ≥ 200 ng/mL, or ≥ 300 ng/mL depending on the cutoff) from negative samples only. The amount of drug detected in a preliminary positive sample cannot be estimated.

Semiquantitative assay
Results of this assay yield only approximate cumulative concentrations of the drug and its metabolites (see Analytical specificity section).

", "Language": "en" }, { "Name": "LimitationInterference", "Value": "

Limitations - interference

See the \"Specific performance data\" section of this document for information on substances tested with this assay. There is the possibility that other substances and/or factors may interfere with the test and cause erroneous results (e.g., technical or procedural errors).

A preliminary positive result with this assay indicates the presence of benzodiazepines and/or their metabolites in urine. It does not reflect the degree of intoxication.

Interfering substances were added to urine containing nordiazepam at ‑25 % and +25 % of the cutoff level at the concentration listed below. Samples were tested and the following results were obtained on a Roche/Hitachi 917 analyzer.

Semiquantitative (ng/mL)

100 ng/mL
Cutoff

200 ng/mL
Cutoff

300 ng/mL
Cutoff

Compound

Cmpd. Conc.

Neg Level

Pos Level

Neg Level

Pos Level

Neg Level

Pos Level

Acetone

1
%

77(NEG)

134(POS)

157(NEG)

260(POS)

231(NEG)

402(POS)

Ascorbic acid

1.5
%

78(NEG)

132(POS)

156(NEG)

262(POS)

233(NEG)

399(POS)

Conjugated bilirubin

0.25
mg/mL

82(NEG)

129(POS)

156(NEG)

247(POS)

229(NEG)

392(POS)

Creatinine

5
mg/mL

81(NEG)

138(POS)

158(NEG)

259(POS)

230(NEG)

396(POS)

Ethanol

1
%

78(NEG)

136(POS)

151(NEG)

261(POS)

228(NEG)

395(POS)

Glucose

20
mg/mL

81(NEG)

138(POS)

158(NEG)

262(POS)

236(NEG)

403(POS)

Hemoglobin

1
mg/mL

76(NEG)

139(POS)

159(NEG)

261(POS)

228(NEG)

398(POS)

Human serum albumin

5
mg/mL

83(NEG)

140(POS)

165(NEG)

273(POS)

243(NEG)

422(POS)

Oxalic acid

2
mg/mL

74(NEG)

128(POS)

151(NEG)

254(POS)

226(NEG)

388(POS)

Sodium chloride

0.5
M

79(NEG)

139(POS)

159(NEG)

262(POS)

234(NEG)

389(POS)

Urea

6
%

80(NEG)

138(POS)

157(NEG)

261(POS)

233(NEG)

405(POS)

The same experiment was performed in the qualitative mode for each cutoff. All negative and positive samples recovered properly in the presence of the interfering substance.

An additional protocol was executed in which samples containing nordiazepam at control levels (±25 % of cutoff) with specific gravities ranging from 1.006 to 1.034 were tested. As with the other interferences, there were no control cross‑overs on any of the 3 assay cutoffs at either extreme specific gravity level.

For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.

ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on cobas c systems. The latest version of the carry‑over evasion list can be found with the NaOHD-SMS-SmpCln1+2-SCCS Method Sheets. For further instructions refer to the operator’s manual. cobas c 502 analyzer: All special wash programming necessary for avoiding carry‑over is available via the cobas link, manual input is required in certain cases.

Where required, special wash/carry‑over evasion programming must be implemented prior to reporting results with this test.

", "Language": "en" }, { "Name": "OrderInformation", "Value": "

OrderInformation (CC Reagents - cobas + Integra)

Order information

Analyzer(s) on which cobas c pack(s) can be used

04939417190

ONLINE DAT Benzodiazepines II (200 tests)

System‑ID 07 6997 5

cobas c 311, cobas c 501/502

Materials required (but not provided):

03304671190

Preciset DAT Plus I calibrators CAL 1‑6 (6 x 5 mL)

Codes 431‑436

03304680190

Preciset DAT Plus II calibrators CAL 1‑6 (6 x 5 mL)

Codes 437‑442

03304698190

C.f.a.s. DAT Qualitative Plus (6 x 5 mL)

04590856190

C.f.a.s. DAT Qualitative Plus Clinical (3 x 5 mL)

Code 699

03312950190

Control Set DAT I (for 300 ng/mL assay)
PreciPos DAT Set I (2 x 10 mL)
PreciNeg DAT Set I (2 x 10 mL)

03312968190

Control Set DAT II (for 100 ng/mL assay)
PreciPos DAT Set II (2 x 10 mL)
PreciNeg DAT Set II (2 x 10 mL)

04500873190

Control Set DAT Clinical (for 100 ng/mL assay)
PreciPos DAT Clinical (2 x 10 mL)
PreciNeg DAT Clinical (2 x 10 mL)

03312976190

Control Set DAT III (for 200 ng/mL assay)
PreciPos DAT Set III (2 x 10 mL)
PreciNeg DAT Set III (2 x 10 mL)

", "Language": "en" }, { "Name": "SystemInformation", "Value": "

System information

For cobas c 311/501 analyzers:

BZ1Q2: ACN 718 (Urine): for qualitative assay, 100 ng/mL

BZ2Q2: ACN 719 (Urine): for qualitative assay, 200 ng/mL

BZ3Q2: ACN 720 (Urine): for qualitative assay, 300 ng/mL

BZ1S2: ACN 728 (Urine): for semiquantitative assay, 100 ng/mL

BZ2S2: ACN 729 (Urine): for semiquantitative assay, 200 ng/mL

BZ3S2: ACN 730 (Urine): for semiquantitative assay, 300 ng/mL

BZQ1C: ACN 727 (Urine): for qualitative assay, 100 ng/mL;
using C.f.a.s. DAT Qualitative Plus Clinical

For cobas c 502 analyzer:

BZ1Q2: ACN 8718 (Urine): for qualitative assay, 100 ng/mL

BZ2Q2: ACN 8719 (Urine): for qualitative assay, 200 ng/mL

BZ3Q2: ACN 8720 (Urine): for qualitative assay, 300 ng/mL

BZ1S2: ACN 8728 (Urine): for semiquantitative assay, 100 ng/mL

BZ2S2: ACN 8729 (Urine): for semiquantitative assay, 200 ng/mL

BZ3S2: ACN 8730 (Urine): for semiquantitative assay, 300 ng/mL

BZQ1C: ACN 8727 (Urine): for qualitative assay, 100 ng/mL;
using C.f.a.s. DAT Qualitative Plus Clinical

", "Language": "en" }, { "Name": "Handling", "Value": "

Reagent handling

Ready for use

Carefully invert reagent container several times prior to use to ensure that the reagent components are mixed.

", "Language": "en" }, { "Name": "TestDefinition", "Value": "

Application for urine

Deselect Automatic Rerun for these applications in the Utility menu, Application screen, Range tab.

cobas c 311 test definitions

Semiquantitative

Qualitative

Assay type

2‑Point End

2‑Point End

Reaction time / Assay points

10 / 10‑31

10 / 10‑31

Wavelength (sub/main)

– /546 nm

– /546 nm

Reaction direction

Increase

Increase

Unit

ng/mL

mAbs

Reagent pipetting

Diluent (H2O)

R1

90 µL

R2

40 µL

Sample volumes

Sample

Sample dilution

100 and 200 ng/mL cutoffs

Sample

Diluent (NaCl)

Normal

4.5 µL

Decreased

4.5 µL

Increased

4.5 µL

300 ng/mL cutoff

Normal

2.0 µL

Decreased

2.0 µL

Increased

2.0 µL

cobas c 501/502 test definitions

Semiquantitative

Qualitative

Assay type

2‑Point End

2‑Point End

Reaction time / Assay points

10 / 16‑46

10 / 16‑46

Wavelength (sub/main)

– /546 nm

– /546 nm

Reaction direction

Increase

Increase

Unit

ng/mL

mAbs

Reagent pipetting

Diluent (H2O)

R1

90 µL

R2

40 µL

Sample volumes

Sample

Sample dilution

100 and 200 ng/mL cutoffs

Sample

Diluent (NaCl)

Normal

4.5 µL

Decreased

4.5 µL

Increased

4.5 µL

300 ng/mL cutoff

Normal

2.0 µL

Decreased

2.0 µL

Increased

2.0 µL

", "Language": "en" }, { "Name": "StorageStability", "Value": "

Storage and stability

Shelf life at 2‑8 °C:

See expiration date on cobas c pack label

On‑board in use and refrigerated on the analyzer:

12 weeks

Do not freeze.

", "Language": "en" }, { "Name": "Calibration", "Value": "

Calibration

Calibrators

Semiquantitative applications

100 and 200 ng/mL cutoff assays

S1‑6: Preciset DAT Plus II calibrators, CAL 1‑6

0, 50, 100, 200, 400, 1000 ng/mL

300 ng/mL cutoff assay

S1-6: Preciset DAT Plus I calibrators, CAL 1‑6

0, 150, 300, 600, 1000, 3000 ng/mL

Qualitative applications

100 ng/mL cutoff assay

S1: Preciset DAT Plus II calibrator - CAL 3 (Test BZ1Q2) , 100 ng/mL, S1: C.f.a.s. DAT Qualitative Plus Clinical (Test BZQ1C) , 100 ng/mL

200 ng/mL cutoff assay

S1: Preciset DAT Plus II calibrator - CAL 4, 200 ng/mL

300 ng/mL cutoff assay

S1: C.f.a.s. DAT Qualitative Plus or Preciset DAT Plus I calibrator - CAL 3, 300 ng/mL

The drug concentrations of the calibrators have been verified by GC‑MS.

Calibration K Factor

For the qualitative applications, enter the K Factor as -1000 into the Calibration menu, Status screen, Calibration Result window.

Calibration mode

Semiquantitative applications

Result Calculation Mode (RCM)

FREFSee Results section.

Qualitative applications

Linear

Calibration frequency

Full (semiquantitative) or blank (qualitative) calibration
• after reagent lot change
• as required following quality control procedures

Calibration interval may be extended based on acceptable verification of calibration by the laboratory.

Traceability: This method has been standardized against a primary reference method (GC‑MS).

", "Language": "en" }, { "Name": "Limitations", "Value": "", "Language": "en" }, { "Name": "PerformanceData", "Value": "

Specific performance data

Representative performance data on the analyzers are given below. Results obtained in individual laboratories may differ.

", "Language": "en" }, { "Name": "Precision", "Value": "

Precision

A nordiazepam solution was added to 5 samples obtained from a human urine sample pool to achieve low, high, and approximate positive and negative control concentrations of drug. These samples were tested for precision in qualitative and semiquantitative modes. Following a CLSI (EP5‑A2) precision protocol, samples were tested in 2 replicates per run, 2 runs per day for 10 days, total n = 40. The following results were obtained on a cobas c 501 analyzer.

Qualitative - 100 ng/mL Cutoff

Drug

Concentration of Sample, ng/mL

Number of Determinations

Results
# Neg /
# Pos

Nordiazepam

57

40

40 Neg / 0 Pos

Nordiazepam

78

40

40 Neg / 0 Pos

Nordiazepam

124

40

0 Neg / 40 Pos

Nordiazepam

190

40

0 Neg / 40 Pos

Nordiazepam

414

40

0 Neg / 40 Pos

Qualitative - 200 ng/mL Cutoff

Drug

Concentration of Sample, ng/mL

Number of Determinations

Results
# Neg /
# Pos

Nordiazepam

102

40

40 Neg / 0 Pos

Nordiazepam

145

40

40 Neg / 0 Pos

Nordiazepam

241

40

0 Neg / 40 Pos

Nordiazepam

419

40

0 Neg / 40 Pos

Nordiazepam

842

40

0 Neg / 40 Pos

Qualitative - 300 ng/mL Cutoff

Drug

Concentration of Sample, ng/mL

Number of Determinations

Results
# Neg /
# Pos

Nordiazepam

148

40

40 Neg / 0 Pos

Nordiazepam

231

40

40 Neg / 0 Pos

Nordiazepam

364

40

0 Neg / 40 Pos

Nordiazepam

615

40

0 Neg / 40 Pos

Nordiazepam

1353

40

0 Neg / 40 Pos

Semiquantitative - 100 ng/mL Cutoff

Drug

Sample Conc., ng/mL

Results# Neg / # Pos

Repeatability

Intermediate Precision

SD,
ng/mL

CV,
%

SD,
ng/mL

CV,
%

Nordiazepam

57

40 / 0

1.9

3.4

2.0

3.5

Nordiazepam

78

40 / 0

2.1

2.7

2.9

3.7

Nordiazepam

124

0 / 40

1.6

1.3

3.8

3.1

Nordiazepam

190

0 / 40

2.9

1.5

3.9

2.0

Nordiazepam

414

0 / 40

3.6

0.9

9.9

2.4

Semiquantitative - 200 ng/mL Cutoff

Drug

Sample Conc., ng/mL

Results# Neg / # Pos

Repeatability

Intermediate Precision

SD,
ng/mL

CV,
%

SD,
ng/mL

CV,
%

Nordiazepam

102

40 / 0

2.5

2.4

3.9

3.8

Nordiazepam

145

40 / 0

1.8

1.3

5.4

3.7

Nordiazepam

241

0 / 40

2.1

0.9

7.5

3.1

Nordiazepam

419

0 / 40

6.6

1.6

12.2

2.9

Nordiazepam

842

0 / 40

8.6

1.0

20.0

2.4

Semiquantitative - 300 ng/mL Cutoff

Drug

Sample Conc., ng/mL

Results# Neg / # Pos

Repeatability

Intermediate Precision

SD,
ng/mL

CV,
%

SD,
ng/mL

CV,
%

Nordiazepam

148

40 / 0

3.7

2.5

4.8

3.3

Nordiazepam

231

40 / 0

4.3

1.9

6.3

2.7

Nordiazepam

364

0 / 40

4.5

1.2

8.2

2.3

Nordiazepam

615

0 / 40

5.8

0.9

15.4

2.5

Nordiazepam

1353

0 / 40

21.4

1.6

35.9

2.7

The data obtained on cobas c 501 analyzer(s) are representative for cobas c 311 analyzer(s).

", "Language": "en" }, { "Name": "MethodComparison", "Value": "", "Language": "en" }, { "Name": "Summary", "Value": "

Summary

The benzodiazepines constitute a class of versatile and widely prescribed central nervous system (CNS) depressant drugs with medically useful anxiolytic, sedative, hypnotic, muscle relaxant, and anticonvulsant activities.

LREFKarch SB, ed. Drug Abuse Handbook. Boca Raton, FL: CRC Press LLC 1998.
,
LREFSalamone SJ, ed. Benzodiazepines and GHB: Detection and Pharmacology. Totowa, NJ: Humana Press 2001.
,
LREFHardman JG, Limbird LE, Gilman A, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw Hill Pub Co. 2001.
,
LREFBaselt RC. Disposition of Toxic Drugs and Chemicals in Man. 7th ed. Foster City, CA: Biomedical Publications 2004.
,
LREFLaurijssens BE, Greenblatt DJ. Pharmacokinetic-pharmacodynamic relationships for benzodiazepines. Clin Pharmacokinet 1996;30:52-76.
The absorption rates, distribution, metabolism, and elimination rates differ significantly among the benzodiazepine derivatives. The quantitative differences in their potencies, pharmacodynamic spectra, and pharmacokinetic properties have led to various therapeutic applications. Clinical distinction of short‑acting versus long‑acting benzodiazepines have been observed in their efficacy, side effect, withdrawal, and dependence potential.
LREFHardman JG, Limbird LE, Gilman A, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw Hill Pub Co. 2001.
,
LREFHallfors DD, Saxe L. The dependence potential of short half-life benzodiazepines: a meta-analysis. Am J Public Health 1993;83:1300-1304.
,
LREFChouinard G. Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound. J Clin Psychiatry 2004:65(5);7-12.
The extensive and efficacious therapeutic use of the benzodiazepines over the last several decades has inadvertently led to their misuse. Benzodiazepine overdoses are frequently associated with co‑administration of drugs of other classes.
LREFAbernethy DR, Greenblatt DJ, Ochs HR, et al. Benzodiazepine drug-drug interactions commonly occurring in clinical practice. Curr Med Res Opin 1984;8:80-93.
,
LREFTanaka E. Toxicological interactions between alcohol and benzodiazepines. J Toxicol Clin Toxicol 2002;40:69-75.
Acute or chronic alcohol ingestion and benzodiazepines co‑administered may lead to various significant toxicological interactions. The net effect may be influenced by internal, external, and pharmacokinetic factors. Abuse patterns may involve relatively low benzodiazepine doses, as well as high‑dose overuse; therefore, urinary drug/metabolite detection requires the proper selection of a cutoff that suits the requirements of the drug testing program.

Following ingestion, the benzodiazepines of the 1,4‑substituted class (including the triazolobenzodiazepine derivatives) are absorbed, metabolized, and excreted in the urine at different rates as a variety of structurally related metabolites. Metabolite diversity reflects the different physiochemical properties and metabolic pathways of the individual drugs. Overall metabolic similarities include removal of substituents from the β ring of the 1,4‑substituted benzodiazepines, α‑hydroxylation of the triazolobenzodiazepines, demethylation, hydroxylation of the three‑position carbon of the β ring, and conjugation of hydroxylated metabolites followed by urinary excretion predominantly as glucuronides.

LREFKarch SB, ed. Drug Abuse Handbook. Boca Raton, FL: CRC Press LLC 1998.
,
LREFSalamone SJ, ed. Benzodiazepines and GHB: Detection and Pharmacology. Totowa, NJ: Humana Press 2001.
,
LREFHardman JG, Limbird LE, Gilman A, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw Hill Pub Co. 2001.
,
LREFBaselt RC. Disposition of Toxic Drugs and Chemicals in Man. 7th ed. Foster City, CA: Biomedical Publications 2004.
,
LREFLaurijssens BE, Greenblatt DJ. Pharmacokinetic-pharmacodynamic relationships for benzodiazepines. Clin Pharmacokinet 1996;30:52-76.
The enzymatic hydrolysis of glucuronidated benzodiazepines can increase their cross‑reactivities to benzodiazepine immunoassays.
LREFDou C, Bournique JS, Zinda MK, et al. Comparison of the Rates of Hydrolysis of Lorazepam-Glucuronide, Oxazepam-Glucuronide and Temazepam-Glucuronide Catalyzed by E. Coli β-D-Glucuronidase Using the OnLine Benzodiazepine Screening Immunoassay on the Roche/Hitachi 917 Analyzer. J of Forensic Science 2001;46(2):335-340.
,
LREFBeck O, Lin Z, Brodin K, et al. The online screening technique for urinary benzodiazepines: comparison with EMIT, FPIA, and GC-MS. J Anal Toxicology 1997;21(7):554-557.
,
LREFSalamone SJ, Honasoge S, Brenner C, et al. Flunitrazepam excretion patterns using the Abuscreen OnTrak and OnLine immunoassays: comparison with GC-MS. J Anal Toxicol 1997;21:341-345.
,
LREFKlette KL, Wiegand RF, Horn CK, et al. Urine benzodiazepine screening using Roche Online KIMS immunoassay with beta-glucuronidase hydrolysis and confirmation by gas chromatography-mass spectrometry. J Anal Toxicol 2005;29:193-200.
,
LREFValentine JL, Middleton R, Sparks C. Identification of urinary benzodiazepines and their metabolites: comparison of automated HPLC and GC-MS after immunoassay screening of clinical specimens. J Anal Toxicol 1996;20(6):416-424.

", "Language": "en" }, { "Name": "Reagents", "Value": "

Reagents - working solutions

R1

Benzodiazepines antibody (sheep polyclonal); buffer; β‑glucuronidase enzyme; bovine serum albumin (BSA); 0.09 % sodium azide

R2

Conjugated benzodiazepine derivative microparticles; buffer; 0.09 % sodium azide

R1 is in position A and R2 is in position B.

", "Language": "en" }, { "Name": "PrecautionsWarnings", "Value": "

Precautions and warnings

For in vitro diagnostic use for health care professionals. Exercise the normal precautions required for handling all laboratory reagents.

Infectious or microbial waste:
Warning: handle waste as potentially biohazardous material. Dispose of waste according to accepted laboratory instructions and procedures.

Environmental hazards:
Apply all relevant local disposal regulations to determine the safe disposal.

Safety data sheet available for professional user on request.

", "Language": "en" }, { "Name": "Caution", "Value": "", "Language": "en" }, { "Name": "QualityControl", "Value": "

Quality control

For quality control, use control materials as listed in the \"Order information\" section.

In addition, other suitable control material can be used.

Drug concentrations of the controls have been verified by GC‑MS.

The control intervals and limits should be adapted to each laboratory’s individual requirements. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.

Follow the applicable government regulations and local guidelines for quality control.

", "Language": "en" }, { "Name": "SpecimenPreparation", "Value": "

Specimen collection and preparation

Only the specimens listed below were tested and found acceptable.

Urine: Collect urine samples in clean glass or plastic containers. Fresh urine specimens do not require any special handling or pretreatment, but an effort should be made to keep pipetted samples free of gross debris. Samples should be within the normal physiological pH range of 5‑8. No additives or preservatives are required. It is recommended that urine specimens be stored at 2‑8 °C and tested within 5 days of collection.

LREFToxicology and Drug Testing in the Clinical Laboratory; Approved Guideline. 2nd ed. (C52-A2). Clinical and Laboratory Standards Institute 2007;27:33.

For prolonged storage, freezing of samples is recommended.

Centrifuge highly turbid specimens before testing.

See the limitations and interferences section for details about possible sample interferences.

Adulteration or dilution of the sample can cause erroneous results. If adulteration is suspected, another sample should be collected. Specimen validity testing is required for specimens collected under the Mandatory Guidelines for Federal Workplace Drug Testing Programs.

LREFMandatory Guidelines for Federal Workplace Drug Testing Programs. Fed Regist 2008 Nov 25;73:71858-71907.

CAUTION: Specimen dilutions should only be used to interpret results of Calc.? and Samp.? alarms, or when estimating concentration in preparation for GC‑MS or LC‑MS/MS. Dilution results are not intended for patient values. Dilution procedures, when used, should be validated.

", "Language": "en" } ] } }, { "ProductSpecVariant": { "MetaData": { "DocumentMaterialNumber": "0204939417190c501", "ProductName": "BNZ2", "ProductLongName": "ONLINE DAT Benzodiazepines II", "Language": "en", "DocumentVersion": "1", "DocumentObjectID": "FF000000060EBB0E", "DocumentOriginID": "FF000000060EBA0E", "MaterialNumbers": [ "04939417190" ], "InstrumentReferences": [ { "ID": "308", "BrandName": "cobas c 311" }, { "ID": "2324", "BrandName": "cobas c 502" }, { "ID": "309", "BrandName": "cobas c 501" } ], "DisclaimerText": "Product information shown on this page contains elements of the officially released Method Sheet. If you require further information please refer to the full Method Sheet PDF under the given link, or contact your local Roche country representative." }, "Chapters": [ { "Name": "IntendedUse", "Value": "

Intended use

Benzodiazepines II (BNZ2) is an in vitro diagnostic test for the qualitative and semiquantitative detection of benzodiazepines in human urine on cobas c systems at cutoff concentrations of 100 ng/mL, 200 ng/mL, and 300 ng/mL.

Semiquantitative test results may be obtained that permit laboratories to assess assay performance as part of a quality control program. Semiquantitative assays are intended to determine an appropriate dilution of the specimen for confirmation by a confirmatory method such as gas chromatography/mass spectrometry (GC-MS), or Liquid Chromatography coupled with Tandem Mass Spectrometry (LC-MS/MS).

Benzodiazepines II provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC‑MS) or Liquid Chromatography coupled with Tandem Mass Spectrometry (LC‑MS/MS) is the preferred confirmatory method.

LREFKarch SB, ed. Drug Abuse Handbook. Boca Raton, FL: CRC Press LLC 1998.
,
LREFSalamone SJ, ed. Benzodiazepines and GHB: Detection and Pharmacology. Totowa, NJ: Humana Press 2001.
Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

", "Language": "en" }, { "Name": "TestPrinciple", "Value": "

Test principle

The assay is based on the kinetic interaction of microparticles in a solution (KIMS)

LREFBeck O, Lin Z, Brodin K, et al. The online screening technique for urinary benzodiazepines: comparison with EMIT, FPIA, and GC-MS. J Anal Toxicology 1997;21(7):554-557.
,
LREFArmbruster DA, Schwarzhoff RH, Hubster EC, et al. Enzyme immunoassay, kinetic microparticle immunoassay, radioimmunoassay, and fluorescence polarization immunoassay compared for drugs-of-abuse screening. Clin Chem 1993;39:2137-2146.
as measured by changes in light transmission. In the absence of sample drug, free antibody binds to drug-microparticle conjugates causing the formation of particle aggregates that are photometrically detected by turbidity measurements. As the aggregation reaction proceeds in the absence of sample drug, the absorbance increases.

When a urine sample contains the drug in question, this drug competes with the particle‑bound drug derivative for free antibody. Antibody bound to sample drug is no longer available to promote particle aggregation, and subsequent particle lattice formation is inhibited. The presence of sample drug diminishes the increasing absorbance in proportion to the concentration of drug in the sample. Sample drug content is determined relative to the value obtained for a known cutoff concentration of drug.

The presence of β‑glucuronidase enzyme enhances the Benzodiazepines II assay cross‑reactivity to some of the glucuronidated metabolites. Enzymatic cleavage makes the benzodiazepine part of the glucuronides more accessible for the antibody.

", "Language": "en" }, { "Name": "MeasuringRange", "Value": "", "Language": "en" }, { "Name": "ExpectedValues", "Value": "

Expected values

Qualitative assay

Results of this assay distinguish preliminary positive (≥ 100 ng/mL, ≥ 200 ng/mL, or ≥ 300 ng/mL depending on the cutoff) from negative samples only. The amount of drug detected in a preliminary positive sample cannot be estimated.

Semiquantitative assay
Results of this assay yield only approximate cumulative concentrations of the drug and its metabolites (see \"Analytical specificity\" section).

", "Language": "en" }, { "Name": "LimitationInterference", "Value": "

Limitations - interference

See the \"Specific performance data\" section of this document for information on substances tested with this assay. There is the possibility that other substances and/or factors may interfere with the test and cause erroneous results (e.g., technical or procedural errors).

A preliminary positive result with this assay indicates the presence of benzodiazepines and/or their metabolites in urine. It does not reflect the degree of intoxication.

In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.

LREFBakker AJ, Mücke M. Gammopathy interference in clinical chemistry assays: mechanisms, detection and prevention. Clin Chem Lab Med 2007;45(9):1240-1243.

For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.

ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on cobas c systems. The latest version of the carry‑over evasion list can be found with the NaOHD-SMS-SmpCln1+2-SCCS Method Sheets. For further instructions refer to the operator’s manual. cobas c 502 analyzer: All special wash programming necessary for avoiding carry‑over is available via the cobas link, manual input is required in certain cases.

Where required, special wash/carry‑over evasion programming must be implemented prior to reporting results with this test.

", "Language": "en" }, { "Name": "OrderInformation", "Value": "

OrderInformation (CC Reagents - cobas + Integra)

Order information

Analyzer(s) on which cobas c pack(s) can be used

04939417190

ONLINE DAT Benzodiazepines II (200 tests)

System‑ID 07 6997 5

cobas c 311, cobas c 501/502

Materials required (but not provided):

03304671190

Preciset DAT Plus I CAL 1‑6 (1 x 5 mL)

Codes 431‑436

03304680190

Preciset DAT Plus II CAL 1‑6 (1 x 5 mL)

Codes 437‑442

03304698190

C.f.a.s. DAT Qualitative Plus (6 x 5 mL)

04590856190

C.f.a.s. DAT Qualitative Plus Clinical (3 x 5 mL)

Code 699

03312950190

Control Set DAT I (for 300 ng/mL assay)
PreciPos DAT Set I (2 x 10 mL)
PreciNeg DAT Set I (2 x 10 mL)

03312968190

Control Set DAT II (for 100 ng/mL assay)
PreciPos DAT Set II (2 x 10 mL)
PreciNeg DAT Set II (2 x 10 mL)

04500873190

Control Set DAT Clinical (for 100 ng/mL assay)
PreciPos DAT Clinical (2 x 10 mL)
PreciNeg DAT Clinical (2 x 10 mL)

03312976190

Control Set DAT III (for 200 ng/mL assay)
PreciPos DAT Set III (2 x 10 mL)
PreciNeg DAT Set III (2 x 10 mL)

", "Language": "en" }, { "Name": "SystemInformation", "Value": "

System information

For cobas c 311/501 analyzers:

BZ1Q2: ACN 718 (Urine): for qualitative assay, 100 ng/mL

BZ2Q2: ACN 719 (Urine): for qualitative assay, 200 ng/mL

BZ3Q2: ACN 720 (Urine): for qualitative assay, 300 ng/mL

BZ1S2: ACN 728 (Urine): for semiquantitative assay, 100 ng/mL

BZ2S2: ACN 729 (Urine): for semiquantitative assay, 200 ng/mL

BZ3S2: ACN 730 (Urine): for semiquantitative assay, 300 ng/mL

BZQ1C: ACN 727 (Urine): for qualitative assay, 100 ng/mL;
using C.f.a.s. DAT Qualitative Plus Clinical

For cobas c 502 analyzer:

BZ1Q2: ACN 8718 (Urine): for qualitative assay, 100 ng/mL

BZ2Q2: ACN 8719 (Urine): for qualitative assay, 200 ng/mL

BZ3Q2: ACN 8720 (Urine): for qualitative assay, 300 ng/mL

BZ1S2: ACN 8728 (Urine): for semiquantitative assay, 100 ng/mL

BZ2S2: ACN 8729 (Urine): for semiquantitative assay, 200 ng/mL

BZ3S2: ACN 8730 (Urine): for semiquantitative assay, 300 ng/mL

BZQ1C: ACN 8727 (Urine): for qualitative assay, 100 ng/mL;
using C.f.a.s. DAT Qualitative Plus Clinical

", "Language": "en" }, { "Name": "Handling", "Value": "

Reagent handling

Ready for use

Carefully invert reagent container several times prior to use to ensure that the reagent components are mixed.

", "Language": "en" }, { "Name": "TestDefinition", "Value": "

Application for urine

Deselect Automatic Rerun for these applications in the Utility menu, Application screen, Range tab.

cobas c 311 test definitions

Semiquantitative

Qualitative

Assay type

2‑Point End

2‑Point End

Reaction time / Assay points

10 / 10‑31

10 / 10‑31

Wavelength (sub/main)

– /546 nm

– /546 nm

Reaction direction

Increase

Increase

Unit

ng/mL

mAbs

Reagent pipetting

Diluent (H2O)

R1

90 µL

R2

40 µL

Sample volumes

Sample

Sample dilution

100 and 200 ng/mL cutoffs

Sample

Diluent (NaCl)

Normal

4.5 µL

Decreased

4.5 µL

Increased

4.5 µL

300 ng/mL cutoff

Normal

2.0 µL

Decreased

2.0 µL

Increased

2.0 µL

cobas c 501/502 test definitions

Semiquantitative

Qualitative

Assay type

2‑Point End

2‑Point End

Reaction time / Assay points

10 / 16‑46

10 / 16‑46

Wavelength (sub/main)

– /546 nm

– /546 nm

Reaction direction

Increase

Increase

Unit

ng/mL

mAbs

Reagent pipetting

Diluent (H2O)

R1

90 µL

R2

40 µL

Sample volumes

Sample

Sample dilution

100 and 200 ng/mL cutoffs

Sample

Diluent (NaCl)

Normal

4.5 µL

Decreased

4.5 µL

Increased

4.5 µL

300 ng/mL cutoff

Normal

2.0 µL

Decreased

2.0 µL

Increased

2.0 µL

", "Language": "en" }, { "Name": "StorageStability", "Value": "

Storage and stability

Shelf life at 2‑8 °C:

See expiration date on cobas c pack label

On‑board in use and refrigerated on the analyzer:

12 weeks

Do not freeze.

", "Language": "en" }, { "Name": "Calibration", "Value": "

Calibration

Calibrators

Semiquantitative applications

100 and 200 ng/mL cutoff assays

S1‑6: Preciset DAT Plus II calibrators, CAL 1‑6

0, 50, 100, 200, 400, 1000 ng/mL

300 ng/mL cutoff assay

S1-6: Preciset DAT Plus I calibrators, CAL 1‑6

0, 150, 300, 600, 1000, 3000 ng/mL

Qualitative applications

100 ng/mL cutoff assay

S1: Preciset DAT Plus II calibrator - CAL 3
(Test BZ1Q2), 100 ng/mL, S1: C.f.a.s. DAT Qualitative Plus Clinical (Test BZQ1C), 100 ng/mL

200 ng/mL cutoff assay

S1: Preciset DAT Plus II calibrator - CAL 4, 200 ng/mL

300 ng/mL cutoff assay

S1: C.f.a.s. DAT Qualitative Plus or Preciset DAT Plus I calibrator - CAL 3, 300 ng/mL

The drug concentrations of the calibrators have been verified by GC‑MS.

Calibration K Factor

For the qualitative applications, enter the K Factor as -1000 into the Calibration menu, Status screen, Calibration Result window.

Calibration mode

Semiquantitative applications

Result Calculation Mode (RCM)

FREFSee Results section.

Qualitative applications

Linear

Calibration frequency

Full (semiquantitative) or blank (qualitative) calibration
• after reagent lot change
• as required following quality control procedures

Calibration interval may be extended based on acceptable verification of calibration by the laboratory.

Traceability: This method has been standardized against a primary reference method (GC‑MS).

", "Language": "en" }, { "Name": "Limitations", "Value": "", "Language": "en" }, { "Name": "PerformanceData", "Value": "

Specific performance data

Representative performance data on the analyzers are given below. These data represent the performance of the analytical procedure itself.

Results obtained in individual laboratories may differ due to heterogeneous sample materials, aging of analyzer components and mixture of reagents running on the analyzer.

", "Language": "en" }, { "Name": "Precision", "Value": "

Precision

Precision was determined using human samples and controls in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP05‑A3 requirements with repeatability (n = 84) and intermediate precision (2 aliquots per run, 2 runs per day, 21 days). Results for repeatability and intermediate precision were obtained on the cobas c 501 analyzer.

Semiquantitative precision - 100 ng/mL

Repeatability

Mean
ng/mL

SD
ng/mL

CV
%

Urine - 50 %

45.0

2.56

5.7

Urine - 25 %

68.8

2.44

3.6

DAT2N

78.8

1.99

2.5

Cutoff urine

99.7

2.38

2.4

Urine + 25 %

123

2.43

2.0

DAT2P

127

2.70

2.1

Urine + 50 %

146

2.59

1.8

Intermediate precision

Mean
ng/mL

SD
ng/mL

CV
%

Urine - 50 %

45.0

2.79

6.2

Urine - 25 %

68.8

2.65

3.9

DAT2N

81.2

3.08

3.8

Cutoff urine

99.7

2.63

2.6

Urine + 25 %

123

2.92

2.4

DAT2P

129

3.40

2.6

Urine + 50 %

146

2.94

2.0

Qualitative precision - 100 ng/mL

Cutoff (100)

Number
tested

Correct
results

Confidence level

Urine - 50 %

84

84

> 95 % negative reading

Urine - 25 %

84

84

> 95 % negative reading

DAT2N

84

84

> 95 % negative reading

Cutoff urine

84

n.a.*

n.a.*

Urine + 25 %

84

84

> 95 % positive reading

DAT2P

84

84

> 95 % positive reading

Urine + 50 %

84

84

> 95 % positive reading

*n.a. = not applicable

Semiquantitative precision - 200 ng/mL

Repeatability

Mean
ng/mL

SD
ng/mL

CV
%

Urine - 50 %

98.2

2.50

2.5

Urine - 25 %

146

2.51

1.7

DAT3N

152

2.70

1.8

Cutoff urine

199

2.48

1.2

Urine + 25 %

242

3.15

1.3

DAT3P

250

2.67

1.1

Urine + 50 %

279

2.34

0.8

Intermediate precision

Mean
ng/mL

SD
ng/mL

CV
%

Urine - 50 %

98.2

3.09

3.1

Urine - 25 %

146

2.87

2.0

DAT3N

150

3.49

2.3

Cutoff urine

199

3.33

1.7

Urine + 25 %

242

3.72

1.5

DAT3P

248

5.68

2.3

Urine + 50 %

279

4.88

1.7

Qualitative precision - 200 ng/mL

Cutoff (200)

Number
tested

Correct
results

Confidence level

Urine - 50 %

84

84

> 95 % negative reading

Urine - 25 %

84

84

> 95 % negative reading

DAT3N

84

84

> 95 % negative reading

Cutoff urine

84

n.a.*

n.a.*

Urine + 25 %

84

84

> 95 % positive reading

DAT3P

84

84

> 95 % positive reading

Urine + 50 %

84

84

> 95 % positive reading

*n.a. = not applicable

Semiquantitative precision - 300 ng/mL

Repeatability

Mean
ng/mL

SD
ng/mL

CV
%

Urine - 50 %

151

4.41

2.9

Urine - 25 %

211

3.99

1.9

DAT1N

223

5.50

2.5

Cutoff urine

276

4.17

1.5

DAT1P

347

4.87

1.4

Urine + 25 %

354

5.21

1.5

Urine + 50 %

432

5.14

1.2

Intermediate precision

Mean
ng/mL

SD
ng/mL

CV
%

Urine - 50 %

151

5.31

3.5

Urine - 25 %

211

5.40

2.6

DAT1N

214

7.23

3.4

Cutoff urine

276

6.07

2.2

DAT1P

347

10.1

2.9

Urine + 25 %

354

6.17

1.7

Urine + 50 %

432

6.70

1.6

Qualitative precision - 300 ng/mL

Cutoff (300)

Number
tested

Correct
results

Confidence level

Urine - 50 %

84

84

> 95 % negative reading

Urine - 25 %

84

84

> 95 % negative reading

DAT1N

84

84

> 95 % negative reading

Cutoff urine

84

n.a.*

n.a.*

DAT1P

84

84

> 95 % positive reading

Urine + 25 %

84

84

> 95 % positive reading

Urine + 50 %

84

84

> 95 % positive reading

*n.a. = not applicable

The data obtained on cobas c 501 analyzer(s) are representative for cobas c 311 analyzer(s).

", "Language": "en" }, { "Name": "MethodComparison", "Value": "", "Language": "en" }, { "Name": "Summary", "Value": "

Summary

The benzodiazepines constitute a class of versatile and widely prescribed central nervous system (CNS) depressant drugs with medically useful anxiolytic, sedative, hypnotic, muscle relaxant, and anticonvulsant activities.

LREFKarch SB, ed. Drug Abuse Handbook. Boca Raton, FL: CRC Press LLC 1998.
,
LREFSalamone SJ, ed. Benzodiazepines and GHB: Detection and Pharmacology. Totowa, NJ: Humana Press 2001.
,
LREFHardman JG, Limbird LE, Gilman A, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw Hill Pub Co. 2001.
,
LREFBaselt RC. Disposition of Toxic Drugs and Chemicals in Man. 7th ed. Foster City, CA: Biomedical Publications 2004.
,
LREFLaurijssens BE, Greenblatt DJ. Pharmacokinetic-pharmacodynamic relationships for benzodiazepines. Clin Pharmacokinet 1996;30:52-76.
The absorption rates, distribution, metabolism, and elimination rates differ significantly among the benzodiazepine derivatives. The quantitative differences in their potencies, pharmacodynamic spectra, and pharmacokinetic properties have led to various therapeutic applications. Clinical distinction of short‑acting versus long‑acting benzodiazepines have been observed in their efficacy, side effect, withdrawal, and dependence potential.
LREFHardman JG, Limbird LE, Gilman A, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw Hill Pub Co. 2001.
,
LREFHallfors DD, Saxe L. The dependence potential of short half-life benzodiazepines: a meta-analysis. Am J Public Health 1993;83:1300-1304.
,
LREFChouinard G. Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound. J Clin Psychiatry 2004:65(5);7-12.
The extensive and efficacious therapeutic use of the benzodiazepines over the last several decades has inadvertently led to their misuse. Benzodiazepine overdoses are frequently associated with co‑administration of drugs of other classes.
LREFAbernethy DR, Greenblatt DJ, Ochs HR, et al. Benzodiazepine drug-drug interactions commonly occurring in clinical practice. Curr Med Res Opin 1984;8:80-93.
,
LREFTanaka E. Toxicological interactions between alcohol and benzodiazepines. J Toxicol Clin Toxicol 2002;40:69-75.
Acute or chronic alcohol ingestion and benzodiazepines co‑administered may lead to various significant toxicological interactions. The net effect may be influenced by internal, external, and pharmacokinetic factors. Abuse patterns may involve relatively low benzodiazepine doses, as well as high‑dose overuse; therefore, urinary drug/metabolite detection requires the proper selection of a cutoff that suits the requirements of the drug testing program.

Following ingestion, the benzodiazepines of the 1,4‑substituted class (including the triazolobenzodiazepine derivatives) are absorbed, metabolized, and excreted in the urine at different rates as a variety of structurally related metabolites. Metabolite diversity reflects the different physiochemical properties and metabolic pathways of the individual drugs. Overall metabolic similarities include removal of substituents from the β ring of the 1,4‑substituted benzodiazepines, α‑hydroxylation of the triazolobenzodiazepines, demethylation, hydroxylation of the three‑position carbon of the β ring, and conjugation of hydroxylated metabolites followed by urinary excretion predominantly as glucuronides.

LREFKarch SB, ed. Drug Abuse Handbook. Boca Raton, FL: CRC Press LLC 1998.
,
LREFSalamone SJ, ed. Benzodiazepines and GHB: Detection and Pharmacology. Totowa, NJ: Humana Press 2001.
,
LREFHardman JG, Limbird LE, Gilman A, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw Hill Pub Co. 2001.
,
LREFBaselt RC. Disposition of Toxic Drugs and Chemicals in Man. 7th ed. Foster City, CA: Biomedical Publications 2004.
,
LREFLaurijssens BE, Greenblatt DJ. Pharmacokinetic-pharmacodynamic relationships for benzodiazepines. Clin Pharmacokinet 1996;30:52-76.
The enzymatic hydrolysis of glucuronidated benzodiazepines can increase their cross‑reactivities to benzodiazepine immunoassays.
LREFDou C, Bournique JS, Zinda MK, et al. Comparison of the Rates of Hydrolysis of Lorazepam-Glucuronide, Oxazepam-Glucuronide and Temazepam-Glucuronide Catalyzed by E. Coli β-D-Glucuronidase Using the OnLine Benzodiazepine Screening Immunoassay on the Roche/Hitachi 917 Analyzer. J of Forensic Science 2001;46(2):335-340.
,
LREFBeck O, Lin Z, Brodin K, et al. The online screening technique for urinary benzodiazepines: comparison with EMIT, FPIA, and GC-MS. J Anal Toxicology 1997;21(7):554-557.
,
LREFSalamone SJ, Honasoge S, Brenner C, et al. Flunitrazepam excretion patterns using the Abuscreen OnTrak and OnLine immunoassays: comparison with GC-MS. J Anal Toxicol 1997;21:341-345.
,
LREFKlette KL, Wiegand RF, Horn CK, et al. Urine benzodiazepine screening using Roche Online KIMS immunoassay with beta-glucuronidase hydrolysis and confirmation by gas chromatography-mass spectrometry. J Anal Toxicol 2005;29:193-200.
,
LREFValentine JL, Middleton R, Sparks C. Identification of urinary benzodiazepines and their metabolites: comparison of automated HPLC and GC-MS after immunoassay screening of clinical specimens. J Anal Toxicol 1996;20(6):416-424.

", "Language": "en" }, { "Name": "Reagents", "Value": "

Reagents - working solutions

R1

Benzodiazepines antibody (sheep polyclonal); buffer; β‑glucuronidase enzyme; bovine serum albumin (BSA); 0.09 % sodium azide

R2

Conjugated benzodiazepine derivative microparticles; buffer; 0.09 % sodium azide

R1 is in position A and R2 is in position B.

", "Language": "en" }, { "Name": "PrecautionsWarnings", "Value": "

Precautions and warnings

For in vitro diagnostic use for health care professionals. Exercise the normal precautions required for handling all laboratory reagents.

Infectious or microbial waste:
Warning: handle waste as potentially biohazardous material. Dispose of waste according to accepted laboratory instructions and procedures.

Environmental hazards:
Apply all relevant local disposal regulations to determine the safe disposal.

Safety data sheet available for professional user on request.

For USA: Caution: Federal law restricts this device to sale by or on the order of a physician.

", "Language": "en" }, { "Name": "Caution", "Value": "", "Language": "en" }, { "Name": "QualityControl", "Value": "

Quality control

For quality control, use control materials as listed in the \"Order information\" section.

In addition, other suitable control material can be used.

Drug concentrations of Control Set DAT I, II, III, and Clinical have been verified by GC‑MS.

The control intervals and limits should be adapted to each laboratory’s individual requirements. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.

Follow the applicable government regulations and local guidelines for quality control.

", "Language": "en" }, { "Name": "SpecimenPreparation", "Value": "

Specimen collection and preparation

Only the specimens listed below were tested and found acceptable.

Urine: Collect urine samples in clean glass or plastic containers. Fresh urine specimens do not require any special handling or pretreatment, but an effort should be made to keep pipetted samples free of gross debris. Samples should be within the normal physiological pH range of 5‑8. No additives or preservatives are required. It is recommended that urine specimens be stored at 2‑8 °C and tested within 5 days of collection.

LREFToxicology and Drug Testing in the Clinical Laboratory; Approved Guideline. 2nd ed. (C52-A2). Clinical and Laboratory Standards Institute 2007;27:33.

Centrifuge highly turbid specimens before testing.

See the limitations and interferences section for details about possible sample interferences.

Sample stability claims were established by experimental data by the manufacturer or based on reference literature and only for the temperatures/time frames as stated in the method sheet. It is the responsibility of the individual laboratory to use all available references and/or its own studies to determine specific stability criteria for its laboratory.

Adulteration or dilution of the sample can cause erroneous results. If adulteration is suspected, another sample should be collected. Specimen validity testing is required for specimens collected under the Mandatory Guidelines for Federal Workplace Drug Testing Programs.

LREFMandatory Guidelines for Federal Workplace Drug Testing Programs. Fed Regist 2017 Jan 23;82:7920-7970.

CAUTION: Specimen dilutions should only be used to interpret results of Calc.? and Samp.? alarms, or when estimating concentration in preparation for GC‑MS or LC‑MS/MS. Dilution results are not intended for patient values. Dilution procedures, when used, should be validated.

", "Language": "en" } ] } }, { "ProductSpecVariant": { "MetaData": { "DocumentMaterialNumber": "0108056927190c503", "ProductName": "BNZ2", "ProductLongName": "ONLINE DAT Benzodiazepines II", "Language": "en", "DocumentVersion": "2", "DocumentObjectID": "FF000000045EBA0E", "DocumentOriginID": "FF0000000381900E", "MaterialNumbers": [ "08056927190" ], "InstrumentReferences": [ { "ID": "8481", "BrandName": "cobas c 503" } ], "DisclaimerText": "Product information shown on this page contains elements of the officially released Method Sheet. If you require further information please refer to the full Method Sheet PDF under the given link, or contact your local Roche country representative." }, "Chapters": [ { "Name": "IntendedUse", "Value": "

Intended use

Benzodiazepines II (BNZ2) is an in vitro diagnostic test for the qualitative and semiquantitative detection of benzodiazepines in human urine on Roche/Hitachi cobas c systems at cutoff concentrations of 100 ng/mL, 200 ng/mL, and 300 ng/mL.

Semiquantitative test results may be obtained that permit laboratories to assess assay performance as part of a quality control program.

Benzodiazepines II provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC‑MS) or Liquid Chromatography coupled with Tandem Mass Spectrometry (LC‑MS/MS) is the preferred confirmatory method.

LREFKarch SB, ed. Drug Abuse Handbook. Boca Raton, FL: CRC Press LLC 1998.
,
LREFSalamone SJ, ed. Benzodiazepines and GHB: Detection and Pharmacology. Totowa, NJ: Humana Press 2001.
Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

", "Language": "en" }, { "Name": "TestPrinciple", "Value": "

Test principle

The assay is based on the kinetic interaction of microparticles in a solution (KIMS)

LREFBeck O, Lin Z, Brodin K, et al. The online screening technique for urinary benzodiazepines: comparison with EMIT, FPIA, and GC-MS. J Anal Toxicology 1997;21(7):554-557.
,
LREFArmbruster DA, Schwarzhoff RH, Hubster EC, et al. Enzyme immunoassay, kinetic microparticle immunoassay, radioimmunoassay, and fluorescence polarization immunoassay compared for drugs-of-abuse screening. Clin Chem 1993;39:2137-2146.
as measured by changes in light transmission. In the absence of sample drug, free antibody binds to drug-microparticle conjugates causing the formation of particle aggregates that are photometrically detected by turbidity measurements. As the aggregation reaction proceeds in the absence of sample drug, the absorbance increases.

When a urine sample contains the drug in question, this drug competes with the particle‑bound drug derivative for free antibody. Antibody bound to sample drug is no longer available to promote particle aggregation, and subsequent particle lattice formation is inhibited. The presence of sample drug diminishes the increasing absorbance in proportion to the concentration of drug in the sample. Sample drug content is determined relative to the value obtained for a known cutoff concentration of drug.

The presence of β‑glucuronidase enzyme enhances the Benzodiazepines II assay cross‑reactivity to some of the glucuronidated metabolites. Enzymatic cleavage makes the benzodiazepine part of glucuronides more accessible for the antibody.

", "Language": "en" }, { "Name": "MeasuringRange", "Value": "", "Language": "en" }, { "Name": "ExpectedValues", "Value": "

Expected values

Qualitative assay

Results of this assay distinguish preliminary positive (≥ 100 ng/mL, ≥ 200 ng/mL, or ≥ 300 ng/mL depending on the cutoff) from negative samples only. The amount of drug detected in a preliminary positive sample cannot be estimated.

Semiquantitative assay
Results of this assay yield only approximate cumulative concentrations of the drug and its metabolites (see Analytical specificity section).

", "Language": "en" }, { "Name": "LimitationInterference", "Value": "

Limitations - interference

See the \"Specific performance data\" section of this document for information on substances tested with this assay. There is the possibility that other substances and/or factors may interfere with the test and cause erroneous results (e.g., technical or procedural errors).

A preliminary positive result with this assay indicates the presence of benzodiazepines and/or their metabolites in urine. It does not reflect the degree of intoxication.

Interfering substances were added to urine containing nordiazepam at ‑25 % and +25 % of the cutoff level at the concentration listed below. Samples were tested and the following results were obtained on a Roche/Hitachi 917 analyzer.

Semiquantitative (ng/mL)

100 ng/mL
cutoff

200 ng/mL
cutoff

300 ng/mL
cutoff

Compound

Cmpd. conc.

Neg level

Pos level

Neg level

Pos level

Neg level

Pos level

Acetone

1
%

77(NEG)

134(POS)

157(NEG)

260(POS)

231(NEG)

402(POS)

Ascorbic acid

1.5
%

78(NEG)

132(POS)

156(NEG)

262(POS)

233(NEG)

399(POS)

Conjugated bilirubin

0.25
mg/mL

82(NEG)

129(POS)

156(NEG)

247(POS)

229(NEG)

392(POS)

Creatinine

5
mg/mL

81(NEG)

138(POS)

158(NEG)

259(POS)

230(NEG)

396(POS)

Ethanol

1
%

78(NEG)

136(POS)

151(NEG)

261(POS)

228(NEG)

395(POS)

Glucose

20
mg/mL

81(NEG)

138(POS)

158(NEG)

262(POS)

236(NEG)

403(POS)

Hemoglobin

1
mg/mL

76(NEG)

139(POS)

159(NEG)

261(POS)

228(NEG)

398(POS)

Human serum albumin

5
mg/mL

83(NEG)

140(POS)

165(NEG)

273(POS)

243(NEG)

422(POS)

Oxalic acid

2
mg/mL

74(NEG)

128(POS)

151(NEG)

254(POS)

226(NEG)

388(POS)

Sodium chloride

0.5
M

79(NEG)

139(POS)

159(NEG)

262(POS)

234(NEG)

389(POS)

Urea

6
%

80(NEG)

138(POS)

157(NEG)

261(POS)

233(NEG)

405(POS)

The same experiment was performed in the qualitative mode for each cutoff. All negative and positive samples recovered properly in the presence of the interfering substance.

An additional protocol was executed in which samples containing nordiazepam at control levels (±25 % of cutoff) with specific gravities ranging from 1.006 to 1.034 were tested. As with the other interferences, there were no control cross‑overs on any of the 3 assay cutoffs at either extreme specific gravity level.

For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.

ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on cobas c systems. All special wash programming necessary for avoiding carry‑over is available via the cobas link. The latest version of the carry‑over evasion list can be found with the NaOHD/SMS/SCCS Method Sheet for information. For further instructions refer to the operator’s manual.

", "Language": "en" }, { "Name": "OrderInformation", "Value": "

OrderInformation (CC Reagents - cobas + Integra)

Order information

Analyzer(s) on which cobas c pack(s) can be used

08056927190

ONLINE DAT Benzodiazepines II (850 tests)

System‑ID 2028 001

cobas c 503

Materials required (but not provided):

03304671190

Preciset DAT Plus I calibrators CAL 1‑6 (6 x 5 mL)

Codes 20431‑20436

03304680190

Preciset DAT Plus II calibrators CAL 1‑6 (6 x 5 mL)

Codes 20437‑20442

03304698190

C.f.a.s. DAT Qualitative Plus (6 x 5 mL)

Code 20698

04590856190

C.f.a.s. DAT Qualitative Plus Clinical (3 x 5 mL)

Code 20699

03312950190

Control Set DAT I (for 300 ng/mL assay)
PreciPos DAT Set I (2 x 10 mL)
PreciNeg DAT Set I (2 x 10 mL)

03312968190

Control Set DAT II (for 100 ng/mL assay)
PreciPos DAT Set II (2 x 10 mL)
PreciNeg DAT Set II (2 x 10 mL)

04500873190

Control Set DAT Clinical (for 100 ng/mL assay)
PreciPos DAT Clinical (2 x 10 mL)
PreciNeg DAT Clinical (2 x 10 mL)

03312976190

Control Set DAT III (for 200 ng/mL assay)
PreciPos DAT Set III (2 x 10 mL)
PreciNeg DAT Set III (2 x 10 mL)

", "Language": "en" }, { "Name": "SystemInformation", "Value": "

System information

BZ1Q2: ACN 20280 (Urine): for qualitative assay, 100 ng/mL

BZ2Q2: ACN 20281 (Urine): for qualitative assay, 200 ng/mL

BZ3Q2: ACN 20282 (Urine): for qualitative assay, 300 ng/mL

BZ1S2: ACN 20284 (Urine): for semiquantitative assay, 100 ng/mL

BZ2S2: ACN 20285 (Urine): for semiquantitative assay, 200 ng/mL

BZ3S2: ACN 20286 (Urine): for semiquantitative assay, 300 ng/mL

BZQ1C: ACN 20283 (Urine): for qualitative assay, 100 ng/mL;
using C.f.a.s. DAT Qualitative Plus Clinical

BZ3‑QP: ACN 20288 (Urine): for qualitative assay, 300 ng/mL; using C.f.a.s. DAT Qualitative Plus

", "Language": "en" }, { "Name": "Handling", "Value": "

Reagent handling

Ready for use

Carefully invert reagent container several times prior to use to ensure that the reagent components are mixed.

", "Language": "en" }, { "Name": "TestDefinition", "Value": "

Application for urine

Semiquantitative

Qualitative

Reporting time

10 min

10 min

Wavelength (sub/main)

– /546 nm

– /546 nm

Reagent pipetting

Diluent (H2O)

R1

63 µL

R2

28 µL

Sample volumes

Sample

Sample dilution

100 and 200 ng/mL cutoffs

Sample

Diluent (NaCl)

Normal

3.2 µL

Decreased

3.2 µL

Increased

3.2 µL

300 ng/mL cutoff

Normal

1.4 µL

Decreased

1.4 µL

Increased

1.4 µL

For further information about the assay test definitions refer to the application parameters setting screen of the corresponding analyzer and assay.

", "Language": "en" }, { "Name": "StorageStability", "Value": "

Storage and stability

Shelf life at 2‑8 °C:

See expiration date on cobas c pack label

On‑board in use and refrigerated on the analyzer:

26 weeks

Do not freeze.

", "Language": "en" }, { "Name": "Calibration", "Value": "

Calibration

Calibrators

Semiquantitative applications

100 and 200 ng/mL cutoff assays

S1‑6: Preciset DAT Plus II calibrators, CAL 1‑6

0, 50, 100, 200, 400, 1000 ng/mL

300 ng/mL cutoff assay

S1-6: Preciset DAT Plus I calibrators, CAL 1‑6

0, 150, 300, 600, 1000, 3000 ng/mL

Qualitative applications

100 ng/mL cutoff assay

S1: Preciset DAT Plus II calibrator - CAL 3 (Test BZ1Q2), 100 ng/mL, S1: C.f.a.s. DAT Qualitative Plus Clinical (Test BZQ1C), 100 ng/mL

200 ng/mL cutoff assay

S1: Preciset DAT Plus II calibrator - CAL 4, 200 ng/mL

300 ng/mL cutoff assay

S1: Preciset DAT Plus I calibrator - CAL 3 (Test BZ3Q2), 300 ng/mL, S1: C.f.a.s. DAT Qualitative Plus (Test BZ3‑QP), 300 ng/mL

The drug concentrations of the calibrators have been verified by GC‑MS.

Calibration K factor

For the qualitative application a K factor of -1000 is predefined in the application settings.

Calibration mode

Semiquantitative applications

Non‑linear

Qualitative applications

Linear

Calibration frequency

Full calibration
- after reagent lot change
- as required following quality control procedures

For the cutoff calibrator a value of \"0\" is encoded in the e‑barcode in order to ensure flagging of positive samples with >Test and negative absorbance values for negative samples.

Calibration interval may be extended based on acceptable verification of calibration by the laboratory.

Traceability: This method has been standardized against a primary reference method (GC‑MS).

", "Language": "en" }, { "Name": "Limitations", "Value": "", "Language": "en" }, { "Name": "PerformanceData", "Value": "

Specific performance data

Representative performance data on the analyzers are given below. These data represent the performance of the analytical procedure itself.

Results obtained in individual laboratories may differ due to heterogenous sample materials, aging of analyzer components and mixture of reagents running on the analyzer.

", "Language": "en" }, { "Name": "Precision", "Value": "

Precision

Precision was determined using human samples and controls in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP05‑A3 requirements with repeatability (n = 84) and intermediate precision (2 aliquots per run, 2 runs per day, 21 days). The following results were obtained:

Semiquantitative precision - 100 ng/mL cutoff

Repeatability

Mean
ng/mL

SD
ng/mL

CV
%

Urine -50 %

49.5

3.30

6.7

DATCN

79.5

3.10

3.9

DAT2N

80.0

3.51

4.4

Cutoff urine

105

3.68

3.5

DAT2P

129

3.38

2.6

DATCP

128

3.51

2.7

Urine +50 %

153

2.98

1.9

Intermediate
precision

Mean
ng/mL

SD
ng/mL

CV
%

Urine -50 %

49.5

4.00

8.1

DATCN

79.5

4.09

5.1

DAT2N

80.0

4.28

5.4

Cutoff urine

105

4.82

4.6

DAT2P

129

4.37

3.4

DATCP

128

4.31

3.4

Urine +50 %

153

4.58

3.0

Qualitative precision - 100 ng/mL cutoff

Cutoff (100)

Number
tested

Correct
results

Confidence level

Urine -50 %

84

84

> 95 % negative reading

DATCN

84

84

> 95 % negative reading

DAT2N

84

84

> 95 % negative reading

Cutoff urine

84

n.a.*

n.a.*

DAT2P

84

84

> 95 % positive reading

DATCP

84

84

> 95 % positive reading

Urine +50 %

84

84

> 95 % positive reading

*n.a. = not applicable

Semiquantitative precision - 200 ng/mL cutoff

Repeatability

Mean
ng/mL

SD
ng/mL

CV
%

Urine -50 %

104

2.49

2.4

DAT3N

152

3.78

2.5

Cutoff urine

200

2.94

1.5

DAT3P

249

3.61

1.4

Urine +50 %

308

2.52

0.8

Intermediate
precision

Mean
ng/mL

SD
ng/mL

CV
%

Urine -50 %

104

4.20

4.0

DAT3N

152

4.31

2.8

Cutoff urine

200

5.85

2.9

DAT3P

249

3.94

1.6

Urine +50 %

308

3.71

1.2

Qualitative precision - 200 ng/mL cutoff

Cutoff (200)

Number
tested

Correct
results

Confidence level

Urine -50 %

84

84

> 95 % negative reading

DAT3N

84

84

> 95 % negative reading

Cutoff urine

84

n.a.*

n.a.*

DAT3P

84

84

> 95 % positive reading

Urine +50 %

84

84

> 95 % positive reading

*n.a. = not applicable

Semiquantitative precision - 300 ng/mL cutoff

Repeatability

Mean
ng/mL

SD
ng/mL

CV
%

Urine -50 %

150

7.03

4.7

DAT1N

231

8.04

3.5

Cutoff urine

345

7.59

2.2

DAT1P

375

7.66

2.0

Urine +50 %

435

8.89

2.0

Intermediate
precision

Mean
ng/mL

SD
ng/mL

CV
%

Urine -50 %

150

10.5

7.0

DAT1N

231

10.0

4.3

Cutoff urine

345

10.6

3.1

DAT1P

375

9.26

2.5

Urine +50 %

435

11.7

2.7

Qualitative precision - 300 ng/mL cutoff

Cutoff (300)

Number
tested

Correct
results

Confidence level

Urine -50 %

84

84

> 95 % negative reading

DAT1N

84

84

> 95 % negative reading

Cutoff urine

84

n.a.*

n.a.*

DAT1P

84

84

> 95 % positive reading

Urine +50 %

84

84

> 95 % positive reading

*n.a. = not applicable

", "Language": "en" }, { "Name": "MethodComparison", "Value": "", "Language": "en" }, { "Name": "Summary", "Value": "

Summary

The benzodiazepines constitute a class of versatile and widely prescribed central nervous system (CNS) depressant drugs with medically useful anxiolytic, sedative, hypnotic, muscle relaxant, and anticonvulsant activities.

LREFKarch SB, ed. Drug Abuse Handbook. Boca Raton, FL: CRC Press LLC 1998.
,
LREFSalamone SJ, ed. Benzodiazepines and GHB: Detection and Pharmacology. Totowa, NJ: Humana Press 2001.
,
LREFHardman JG, Limbird LE, Gilman A, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw Hill Pub Co. 2001.
,
LREFBaselt RC. Disposition of Toxic Drugs and Chemicals in Man. 7th ed. Foster City, CA: Biomedical Publications 2004.
,
LREFLaurijssens BE, Greenblatt DJ. Pharmacokinetic-pharmacodynamic relationships for benzodiazepines. Clin Pharmacokinet 1996;30:52-76.
The absorption rates, distribution, metabolism, and elimination rates differ significantly among the benzodiazepine derivatives. The quantitative differences in their potencies, pharmacodynamic spectra, and pharmacokinetic properties have led to various therapeutic applications. Clinical distinction of short‑acting versus long‑acting benzodiazepines have been observed in their efficacy, side effect, withdrawal, and dependence potential.
LREFHardman JG, Limbird LE, Gilman A, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw Hill Pub Co. 2001.
,
LREFHallfors DD, Saxe L. The dependence potential of short half-life benzodiazepines: a meta-analysis. Am J Public Health 1993;83:1300-1304.
,
LREFChouinard G. Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound. J Clin Psychiatry 2004:65(5);7-12.
The extensive and efficacious therapeutic use of the benzodiazepines over the last several decades has inadvertently led to their misuse. Benzodiazepine overdoses are frequently associated with co‑administration of drugs of other classes.
LREFAbernethy DR, Greenblatt DJ, Ochs HR, et al. Benzodiazepine drug-drug interactions commonly occurring in clinical practice. Curr Med Res Opin 1984;8:80-93.
,
LREFTanaka E. Toxicological interactions between alcohol and benzodiazepines. J Toxicol Clin Toxicol 2002;40:69-75.
Acute or chronic alcohol ingestion and benzodiazepines co‑administered may lead to various significant toxicological interactions. The net effect may be influenced by internal, external, and pharmacokinetic factors. Abuse patterns may involve relatively low benzodiazepine doses, as well as high‑dose overuse; therefore, urinary drug/metabolite detection requires the proper selection of a cutoff that suits the requirements of the drug testing program.

Following ingestion, the benzodiazepines of the 1,4‑substituted class (including the triazolobenzodiazepine derivatives) are absorbed, metabolized, and excreted in the urine at different rates as a variety of structurally related metabolites. Metabolite diversity reflects the different physiochemical properties and metabolic pathways of the individual drugs. Overall metabolic similarities include removal of substituents from the β ring of the 1,4‑substituted benzodiazepines, α‑hydroxylation of the triazolobenzodiazepines, demethylation, hydroxylation of the three‑position carbon of the β ring, and conjugation of hydroxylated metabolites followed by urinary excretion predominantly as glucuronides.

LREFKarch SB, ed. Drug Abuse Handbook. Boca Raton, FL: CRC Press LLC 1998.
,
LREFSalamone SJ, ed. Benzodiazepines and GHB: Detection and Pharmacology. Totowa, NJ: Humana Press 2001.
,
LREFHardman JG, Limbird LE, Gilman A, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw Hill Pub Co. 2001.
,
LREFBaselt RC. Disposition of Toxic Drugs and Chemicals in Man. 7th ed. Foster City, CA: Biomedical Publications 2004.
,
LREFLaurijssens BE, Greenblatt DJ. Pharmacokinetic-pharmacodynamic relationships for benzodiazepines. Clin Pharmacokinet 1996;30:52-76.
The enzymatic hydrolysis of glucuronidated benzodiazepines can increase their cross‑reactivities to benzodiazepine immunoassays.
LREFDou C, Bournique JS, Zinda MK, et al. Comparison of the Rates of Hydrolysis of Lorazepam-Glucuronide, Oxazepam-Glucuronide and Temazepam-Glucuronide Catalyzed by E. Coli β-D-Glucuronidase Using the OnLine Benzodiazepine Screening Immunoassay on the Roche/Hitachi 917 Analyzer. J of Forensic Science 2001;46(2):335-340.
,
LREFBeck O, Lin Z, Brodin K, et al. The online screening technique for urinary benzodiazepines: comparison with EMIT, FPIA, and GC-MS. J Anal Toxicology 1997;21(7):554-557.
,
LREFSalamone SJ, Honasoge S, Brenner C, et al. Flunitrazepam excretion patterns using the Abuscreen OnTrak and OnLine immunoassays: comparison with GC-MS. J Anal Toxicol 1997;21:341-345.
,
LREFKlette KL, Wiegand RF, Horn CK, et al. Urine benzodiazepine screening using Roche Online KIMS immunoassay with beta-glucuronidase hydrolysis and confirmation by gas chromatography-mass spectrometry. J Anal Toxicol 2005;29:193-200.
,
LREFValentine JL, Middleton R, Sparks C. Identification of urinary benzodiazepines and their metabolites: comparison of automated HPLC and GC-MS after immunoassay screening of clinical specimens. J Anal Toxicol 1996;20(6):416-424.

", "Language": "en" }, { "Name": "Reagents", "Value": "

Reagents - working solutions

R1

Benzodiazepines antibody (sheep polyclonal); buffer; β‑glucuronidase enzyme; bovine serum albumin (BSA); 0.09 % sodium azide

R2

Conjugated benzodiazepine derivative microparticles; buffer; 0.09 % sodium azide

R1 is in position B and R2 is in position C.

", "Language": "en" }, { "Name": "PrecautionsWarnings", "Value": "

Precautions and warnings

For in vitro diagnostic use for health care professionals. Exercise the normal precautions required for handling all laboratory reagents.

Infectious or microbial waste:
Warning: handle waste as potentially biohazardous material. Dispose of waste according to accepted laboratory instructions and procedures.

Environmental hazards:
Apply all relevant local disposal regulations to determine the safe disposal.

Safety data sheet available for professional user on request.

", "Language": "en" }, { "Name": "Caution", "Value": "", "Language": "en" }, { "Name": "QualityControl", "Value": "

Quality control

For quality control, use control materials as listed in the “Order information” section. In addition, other suitable control material can be used.

Drug concentrations of Control Set DAT I, II, III and Clinical have been verified by GC‑MS.

The control intervals and limits should be adapted to each laboratory’s individual requirements. It is recommended to perform quality control always after lot calibration and subsequently at least every 26 weeks.

Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.

Follow the applicable government regulations and local guidelines for quality control.

", "Language": "en" }, { "Name": "SpecimenPreparation", "Value": "

Specimen collection and preparation

Only the specimens listed below were tested and found acceptable.

Urine: Collect urine samples in clean glass or plastic containers. Fresh urine specimens do not require any special handling or pretreatment, but an effort should be made to keep pipetted samples free of gross debris. Samples should be within the normal physiological pH range of 5‑8. No additives or preservatives are required. It is recommended that urine specimens be stored at 2‑8 °C and tested within 5 days of collection.

LREFToxicology and Drug Testing in the Clinical Laboratory; Approved Guideline. 2nd ed. (C52-A2). Clinical and Laboratory Standards Institute 2007;27:33.

For prolonged storage, freezing of samples is recommended.

Centrifuge highly turbid specimens before testing.

See the limitations and interferences section for details about possible sample interferences.

Adulteration or dilution of the sample can cause erroneous results. If adulteration is suspected, another sample should be collected. Specimen validity testing is required for specimens collected under the Mandatory Guidelines for Federal Workplace Drug Testing Programs.

LREFMandatory Guidelines for Federal Workplace Drug Testing Programs. Fed Regist 2017 Jan 23;82:7920-7970.

CAUTION: Specimen dilutions should only be used to interpret results of Calc.? and Samp.? alarms, or when estimating concentration in preparation for GC‑MS or LC‑MS/MS. Dilution results are not intended for patient values. Dilution procedures, when used, should be validated.

", "Language": "en" } ] } }, { "ProductSpecVariant": { "MetaData": { "DocumentMaterialNumber": "1708056927190c503sp", "ProductName": "BNZ2", "ProductLongName": "ONLINE DAT Benzodiazepines II", "Language": "en", "DocumentVersion": "3", "DocumentObjectID": "FF000000045F240E", "DocumentOriginID": "FF0000000377BE0E", "MaterialNumbers": [ "08056927190" ], "InstrumentReferences": [ { "ID": "8481", "BrandName": "cobas c 503" } ], "DisclaimerText": "Product information shown on this page contains elements of the officially released Method Sheet. If you require further information please refer to the full Method Sheet PDF under the given link, or contact your local Roche country representative." }, "Chapters": [ { "Name": "IntendedUse", "Value": "

Intended use

ONLINE DAT Benzodiazepines II (BNZ2) is an in vitro diagnostic test for the qualitative detection of benzodiazepines in human serum and plasma on Roche/Hitachi cobas c systems at a cutoff concentration of 200 ng/mL.

Benzodiazepines II provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC‑MS) or Liquid Chromatography coupled with Tandem Mass Spectrometry (LC‑MS/MS) is the preferred confirmatory method.

LREFKarch SB, ed. Drug Abuse Handbook. Boca Raton, FL: CRC Press LLC 1998.
,
LREFSalamone SJ, ed. Benzodiazepines and GHB: Detection and Pharmacology. Totowa, NJ: Humana Press 2001.
Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

", "Language": "en" }, { "Name": "TestPrinciple", "Value": "

Test principle

The assay is based on the kinetic interaction of microparticles in a solution (KIMS)

LREFBeck O, Lin Z, Brodin K, et al. The online screening technique for urinary benzodiazepines: comparison with EMIT, FPIA, and GC-MS. J Anal Toxicology 1997;21(7):554-557.
,
LREFArmbruster DA, Schwarzhoff RH, Hubster EC, et al. Enzyme immunoassay, kinetic microparticle immunoassay, radioimmunoassay, and fluorescence polarization immunoassay compared for drugs-of-abuse screening. Clin Chem 1993;39:2137-2146.
as measured by changes in light transmission. In the absence of sample drug, free antibody binds to drug-microparticle conjugates causing the formation of particle aggregates that are photometrically detected by turbidity measurements. As the aggregation reaction proceeds in the absence of sample drug, the absorbance increases.

When a serum sample contains the drug in question, this drug competes with the particle‑bound drug derivative for free antibody. Antibody bound to sample drug is no longer available to promote particle aggregation, and subsequent particle lattice formation is inhibited. The presence of sample drug diminishes the increasing absorbance in proportion to the concentration of drug in the sample. Sample drug content is determined relative to the value obtained for a known cutoff concentration of drug.

The presence of β‑glucuronidase enzyme enhances the Benzodiazepines II assay cross‑reactivity to some of the glucuronidated metabolites. Enzymatic cleavage makes the benzodiazepine part of the glucuronides more accessible for the antibody.

", "Language": "en" }, { "Name": "MeasuringRange", "Value": "", "Language": "en" }, { "Name": "ExpectedValues", "Value": "

Expected values

Qualitative assay

Results of this assay distinguish preliminary positive (≥ 200 ng/mL) from negative samples only. The amount of drug detected in a preliminary positive sample cannot be estimated.

", "Language": "en" }, { "Name": "LimitationInterference", "Value": "

Limitations - interference

Criterion: No cross‑over at initial values of samples of 100 ng/mL and 300 ng/mL (control levels).

See the \"Specific performance data\" section of this document for information on substances tested with this assay. There is the possibility that other substances and/or factors may interfere with the test and cause erroneous results (e.g., technical or procedural errors).

A preliminary positive result with this assay indicates the presence of benzodiazepines and/or their metabolites in serum. It does not reflect the degree of intoxication.

Icterus:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an I index of 60 for conjugated and unconjugated bilirubin (approximate conjugated and unconjugated bilirubin concentration: 1026 µmol/L or 60 mg/dL).

Hemolysis:

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an H index of 1000 (approximate hemoglobin concentration: 622 µmol/L or 1000 mg/dL).

Lipemia (Intralipid):

LREFGlick MR, Ryder KW, Jackson SA. Graphical Comparisons of Interferences in Clinical Chemistry Instrumentation. Clin Chem 1986;32:470-475.
No significant interference up to an L index of 2000. There is poor correlation between the L index (corresponds to turbidity) and triglycerides concentration.

Rheumatoid factors: No significant interference from rheumatoid factors up to a concentration of 1200 IU/mL.

Immunoglobulins: No significant interference from immunoglobulins up to a concentration of 16 g/L (simulated by human immunoglobulin A), up to a concentration of 70 g/L (simulated by human immunoglobulin G) and up to a concentration of 10 g/L (simulated by human immunoglobulin M).

Albumin: No significant interference from human serum albumin up to a concentration of 70 g/L.

For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.

ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on cobas c systems. All special wash programming necessary for avoiding carry‑over is available via the cobas link. The latest version of the carry‑over evasion list can be found with the NaOHD/SMS/SCCS Method Sheet for information. For further instructions refer to the operator’s manual.

", "Language": "en" }, { "Name": "OrderInformation", "Value": "

OrderInformation (CC Reagents - cobas + Integra)

Order information

Analyzer(s) on which cobas c pack(s) can be used

08056927190

ONLINE DAT Benzodiazepines II (850 tests)

System‑ID 2028 001

cobas c 503

Materials required (but not provided):

03304671190

Preciset DAT Plus I calibrator CAL 5

Code 20435

07978766190

Serum DAT Control Low (ACQ Partner Channel*)

07978740190

Serum DAT Control High (ACQ Partner Channel*)

08063494190

NaCl Diluent 9 % (123 mL)

System‑ID 2906 001

*Roche does not hold the product registration for Partner Channels. The legal manufacturer indicated on the kit is solely responsible for all of the design, legal, and regulatory aspects of the product.

", "Language": "en" }, { "Name": "SystemInformation", "Value": "

System information

BEQ2S: ACN 20287 (Serum/plasma): for qualitative assay, 200 ng/mL

", "Language": "en" }, { "Name": "Handling", "Value": "

Reagent handling

Ready for use

Carefully invert reagent container several times prior to use to ensure that the reagent components are mixed.

", "Language": "en" }, { "Name": "TestDefinition", "Value": "

Application for serum and plasma

Test definition

Qualitative

Reporting time

10 min

Wavelength (sub/main)

– /546 nm

Reagent pipetting

R1

63 µL

R2

28 µL

Sample volumes

Sample

200 ng/mL cutoff

Normal

3.2 µL

Decreased

3.2 µL

Increased

3.2 µL

For further information about the assay test definitions refer to the application parameters setting screen of the corresponding analyzer and assay.

", "Language": "en" }, { "Name": "StorageStability", "Value": "

Storage and stability

Shelf life at 2‑8 °C:

See expiration date on cobas c pack label

On‑board in use and refrigerated on the analyzer:

26 weeks

Do not freeze.

", "Language": "en" }, { "Name": "Calibration", "Value": "

Calibration

Calibrators

Qualitative application

200 ng/mL cutoff assay

S1: Preciset DAT Plus I calibrator ‑ CAL 5, 1000 ng/mL with automatic pre‑dilution

The drug concentration of the calibrator has been verified by GC‑MS.

Calibration K factor

For the qualitative application a K factor of -1000 is predefined in the application settings.

Calibration mode

Qualitative application

Linear

Calibration frequency

Full calibration
- after reagent lot change
- as required following quality control procedures

For the cutoff calibrator a value of \"0\" is encoded in the e‑barcode in order to ensure flagging of positive samples with >Test and negative absorbance values for negative samples.

Calibration interval may be extended based on acceptable verification of calibration by the laboratory.

Traceability: This method has been standardized against a primary reference method (GC‑MS).

", "Language": "en" }, { "Name": "Limitations", "Value": "", "Language": "en" }, { "Name": "PerformanceData", "Value": "

Specific performance data

Representative performance data on the analyzers are given below. These data represent the performance of the analytical procedure itself.

Results obtained in individual laboratories may differ due to heterogenous sample materials, aging of analyzer components and mixture of reagents running on the analyzer.

", "Language": "en" }, { "Name": "Precision", "Value": "

Precision

Precision was determined using human samples and controls in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP05‑A3 requirements with repeatability (n = 84) and intermediate precision (2 aliquots per run, 2 runs per day, 21 days). The following results were obtained:

Cutoff (200)

Number
tested

Correct
results

Confidence level

Serum -75 %

84

84

> 95 % negative reading

ACQ‑L

84

84

> 95 % negative reading

Cutoff serum

84

n.a.**

n.a.**

ACQ‑H

84

84

> 95 % positive reading

Serum +75 %

84

84

> 95 % positive reading

**n.a. = not applicable

", "Language": "en" }, { "Name": "MethodComparison", "Value": "", "Language": "en" }, { "Name": "Summary", "Value": "

Summary

The benzodiazepines constitute a class of versatile and widely prescribed central nervous system (CNS) depressant drugs with medically useful anxiolytic, sedative, hypnotic, muscle relaxant, and anticonvulsant activities.

LREFKarch SB, ed. Drug Abuse Handbook. Boca Raton, FL: CRC Press LLC 1998.
,
LREFSalamone SJ, ed. Benzodiazepines and GHB: Detection and Pharmacology. Totowa, NJ: Humana Press 2001.
,
LREFHardman JG, Limbird LE, Gilman A, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw Hill Pub Co. 2001.
,
LREFBaselt RC. Disposition of Toxic Drugs and Chemicals in Man. 7th ed. Foster City, CA: Biomedical Publications 2004.
,
LREFLaurijssens BE, Greenblatt DJ. Pharmacokinetic-pharmacodynamic relationships for benzodiazepines. Clin Pharmacokinet 1996;30:52-76.
The absorption rates, distribution, metabolism, and elimination rates differ significantly among the benzodiazepine derivatives. The quantitative differences in their potencies, pharmacodynamic spectra, and pharmacokinetic properties have led to various therapeutic applications. Clinical distinction of short‑acting versus long‑acting benzodiazepines have been observed in their efficacy, side effect, withdrawal, and dependence potential.
LREFHardman JG, Limbird LE, Gilman A, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw Hill Pub Co. 2001.
,
LREFHallfors DD, Saxe L. The dependence potential of short half-life benzodiazepines: a meta-analysis. Am J Public Health 1993;83:1300-1304.
,
LREFChouinard G. Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound. J Clin Psychiatry 2004:65(5);7-12.
The extensive and efficacious therapeutic use of the benzodiazepines over the last several decades has inadvertently led to their misuse. Benzodiazepine overdoses are frequently associated with co‑administration of drugs of other classes.
LREFAbernethy DR, Greenblatt DJ, Ochs HR, et al. Benzodiazepine drug-drug interactions commonly occurring in clinical practice. Curr Med Res Opin 1984;8:80-93.
,
LREFTanaka E. Toxicological interactions between alcohol and benzodiazepines. J Toxicol Clin Toxicol 2002;40:69-75.
Acute or chronic alcohol ingestion and benzodiazepines co‑administered may lead to various significant toxicological interactions. The net effect may be influenced by internal, external, and pharmacokinetic factors. Abuse patterns may involve relatively low benzodiazepine doses, as well as high‑dose overuse.

Following ingestion, the benzodiazepines of the 1,4‑substituted class (including the triazolobenzodiazepine derivatives) are absorbed, metabolized, and excreted in the urine at different rates as a variety of structurally related metabolites. Metabolite diversity reflects the different physiochemical properties and metabolic pathways of the individual drugs. Overall metabolic similarities include removal of substituents from the β ring of the 1,4‑substituted benzodiazepines, α‑hydroxylation of the triazolobenzodiazepines, demethylation, hydroxylation of the three‑position carbon of the β ring, and conjugation of hydroxylated metabolites followed by urinary excretion predominantly as glucuronides.

LREFKarch SB, ed. Drug Abuse Handbook. Boca Raton, FL: CRC Press LLC 1998.
,
LREFSalamone SJ, ed. Benzodiazepines and GHB: Detection and Pharmacology. Totowa, NJ: Humana Press 2001.
,
LREFHardman JG, Limbird LE, Gilman A, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw Hill Pub Co. 2001.
,
LREFBaselt RC. Disposition of Toxic Drugs and Chemicals in Man. 7th ed. Foster City, CA: Biomedical Publications 2004.
,
LREFLaurijssens BE, Greenblatt DJ. Pharmacokinetic-pharmacodynamic relationships for benzodiazepines. Clin Pharmacokinet 1996;30:52-76.
The enzymatic hydrolysis of glucuronidated benzodiazepines can increase their cross‑reactivities to benzodiazepine immunoassays.
LREFDou C, Bournique JS, Zinda MK, et al. Comparison of the Rates of Hydrolysis of Lorazepam-Glucuronide, Oxazepam-Glucuronide and Temazepam-Glucuronide Catalyzed by E. Coli β-D-Glucuronidase Using the OnLine Benzodiazepine Screening Immunoassay on the Roche/Hitachi 917 Analyzer. J of Forensic Science 2001;46(2):335-340.
,
LREFBeck O, Lin Z, Brodin K, et al. The online screening technique for urinary benzodiazepines: comparison with EMIT, FPIA, and GC-MS. J Anal Toxicology 1997;21(7):554-557.
,
LREFSalamone SJ, Honasoge S, Brenner C, et al. Flunitrazepam excretion patterns using the Abuscreen OnTrak and OnLine immunoassays: comparison with GC-MS. J Anal Toxicol 1997;21:341-345.
,
LREFKlette KL, Wiegand RF, Horn CK, et al. Urine benzodiazepine screening using Roche Online KIMS immunoassay with beta-glucuronidase hydrolysis and confirmation by gas chromatography-mass spectrometry. J Anal Toxicol 2005;29:193-200.
,
LREFValentine JL, Middleton R, Sparks C. Identification of urinary benzodiazepines and their metabolites: comparison of automated HPLC and GC-MS after immunoassay screening of clinical specimens. J Anal Toxicol 1996;20(6):416-424.

", "Language": "en" }, { "Name": "Reagents", "Value": "

Reagents - working solutions

R1

Benzodiazepines antibody (sheep polyclonal); buffer; β‑glucuronidase enzyme; bovine serum albumin (BSA); 0.09 % sodium azide

R2

Conjugated benzodiazepine derivative microparticles; buffer; 0.09 % sodium azide

R1 is in position B and R2 is in position C.

", "Language": "en" }, { "Name": "PrecautionsWarnings", "Value": "

Precautions and warnings

For in vitro diagnostic use for health care professionals. Exercise the normal precautions required for handling all laboratory reagents.

Infectious or microbial waste:
Warning: handle waste as potentially biohazardous material. Dispose of waste according to accepted laboratory instructions and procedures.

Environmental hazards:
Apply all relevant local disposal regulations to determine the safe disposal.

Safety data sheet available for professional user on request.

", "Language": "en" }, { "Name": "Caution", "Value": "", "Language": "en" }, { "Name": "QualityControl", "Value": "

Quality control

For quality control, use control materials as listed in the “Order information” section. In addition, other suitable control material can be used.

Drug concentrations of the high and low controls have been verified by GC‑MS.

The control intervals and limits should be adapted to each laboratory’s individual requirements. It is recommended to perform quality control always after lot calibration and subsequently at least every 26 weeks.

Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.

Follow the applicable government regulations and local guidelines for quality control.

", "Language": "en" }, { "Name": "SpecimenPreparation", "Value": "

Specimen collection and preparation

For specimen collection and preparation only use suitable tubes or collection containers.

Only the specimens listed below were tested and found acceptable.
Serum: Serum tubes with and without separating gel.
Plasma: K2‑ or K3‑EDTA, lithium heparin plasma.

Stability:

5 days capped at 15‑25 °C

14 days capped at 2‑8 °C

6 months capped at -20 °C

The sample types listed were tested with a selection of sample collection tubes that were commercially available at the time of testing, i.e. not all available tubes of all manufacturers were tested. Sample collection systems from various manufacturers may contain differing materials which could affect the test results in some cases. When processing samples in primary tubes (sample collection systems), follow the instructions of the tube manufacturer.

Centrifuge samples containing precipitates before performing the assay.

See the limitations and interferences section for details about possible sample interferences.

Specimens can be repeatedly frozen and thawed up to 3 times.

Invert thawed specimens several times prior to testing.

CAUTION: Specimen dilutions should only be used to interpret results of Calc.? and Samp.? alarms, or when estimating concentration in preparation for GC‑MS or LC‑MS/MS. Dilution results are not intended for patient values. Dilution procedures, when used, should be validated.

", "Language": "en" } ] } }, { "ProductSpecVariant": { "MetaData": { "DocumentMaterialNumber": "0106334415190c701", "ProductName": "BNZ2", "ProductLongName": "ONLINE DAT Benzodiazepines II", "Language": "en", "DocumentVersion": "5", "DocumentObjectID": "FF000000045EBC0E", "DocumentOriginID": "FF00000000585D0E", "MaterialNumbers": [ "06334415190" ], "InstrumentReferences": [ { "ID": "2492", "BrandName": "cobas c 702" }, { "ID": "310", "BrandName": "cobas c 701" } ], "DisclaimerText": "Product information shown on this page contains elements of the officially released Method Sheet. If you require further information please refer to the full Method Sheet PDF under the given link, or contact your local Roche country representative." }, "Chapters": [ { "Name": "IntendedUse", "Value": "

Intended use

Benzodiazepines II (BNZ2) is an in vitro diagnostic test for the qualitative and semiquantitative detection of benzodiazepines in human urine on Roche/Hitachi cobas c systems at cutoff concentrations of 100 ng/mL, 200 ng/mL, and 300 ng/mL.

Semiquantitative test results may be obtained that permit laboratories to assess assay performance as part of a quality control program.

Benzodiazepines II provides only a preliminary analytical test result. A more specific alternate chemical method must be used in order to obtain a confirmed analytical result. Gas chromatography/mass spectrometry (GC‑MS) or Liquid Chromatography coupled with Tandem Mass Spectrometry (LC‑MS/MS) is the preferred confirmatory method.

LREFKarch SB, ed. Drug Abuse Handbook. Boca Raton, FL: CRC Press LLC 1998.
,
LREFSalamone SJ, ed. Benzodiazepines and GHB: Detection and Pharmacology. Totowa, NJ: Humana Press 2001.
Clinical consideration and professional judgment should be applied to any drug of abuse test result, particularly when preliminary positive results are used.

", "Language": "en" }, { "Name": "TestPrinciple", "Value": "

Test principle

The assay is based on the kinetic interaction of microparticles in a solution (KIMS)

LREFBeck O, Lin Z, Brodin K, et al. The online screening technique for urinary benzodiazepines: comparison with EMIT, FPIA, and GC-MS. J Anal Toxicology 1997;21(7):554-557.
,
LREFArmbruster DA, Schwarzhoff RH, Hubster EC, et al. Enzyme immunoassay, kinetic microparticle immunoassay, radioimmunoassay, and fluorescence polarization immunoassay compared for drugs-of-abuse screening. Clin Chem 1993;39:2137-2146.
as measured by changes in light transmission. In the absence of sample drug, free antibody binds to drug‑microparticle conjugates causing the formation of particle aggregates that are photometrically detected by turbidity measurements. As the aggregation reaction proceeds in the absence of sample drug, the absorbance increases.

When a urine sample contains the drug in question, this drug competes with the particle‑bound drug derivative for free antibody. Antibody bound to sample drug is no longer available to promote particle aggregation, and subsequent particle lattice formation is inhibited. The presence of sample drug diminishes the increasing absorbance in proportion to the concentration of drug in the sample. Sample drug content is determined relative to the value obtained for a known cutoff concentration of drug.

The presence of β‑glucuronidase enzyme enhances the Benzodiazepines II assay cross‑reactivity to some of the glucuronidated metabolites. Enzymatic cleavage makes the benzodiazepine part of the glucuronides more accessible for the antibody.

", "Language": "en" }, { "Name": "MeasuringRange", "Value": "", "Language": "en" }, { "Name": "ExpectedValues", "Value": "

Expected values

Qualitative assay

Results of this assay distinguish preliminary positive (≥ 100 ng/mL, ≥ 200 ng/mL, or ≥ 300 ng/mL depending on the cutoff) from negative samples only. The amount of drug detected in a preliminary positive sample cannot be estimated.

Semiquantitative assay
Results of this assay yield only approximate cumulative concentrations of the drug and its metabolites (see Analytical specificity section).

", "Language": "en" }, { "Name": "LimitationInterference", "Value": "

Limitations - interference

See the \"Specific performance data\" section of this document for information on substances tested with this assay. There is the possibility that other substances and/or factors may interfere with the test and cause erroneous results (e.g., technical or procedural errors).

A preliminary positive result with this assay indicates the presence of benzodiazepines

and/or their metabolites in urine. It does not reflect the degree of intoxication.

Interfering substances were added to urine containing nordiazepam at ‑25 % and +25 % of the cutoff level at the concentration listed below. Samples were tested and the following results were obtained on a Roche/Hitachi 917 analyzer.

Semiquantitative (ng/mL)

100 ng/mL Cutoff

200 ng/mL Cutoff

300 ng/mL Cutoff

Compound

Cmpd. Conc.

Neg Level

Pos Level

Neg Level

Pos Level

Neg Level

Pos Level

Acetone

1
%

77(NEG)

134(POS)

157(NEG)

260(POS)

231(NEG)

402(POS)

Ascorbic acid

1.5
%

78(NEG)

132(POS)

156(NEG)

262(POS)

233(NEG)

399(POS)

Conjugated bilirubin

0.25
mg/mL

82(NEG)

129(POS)

156(NEG)

247(POS)

229(NEG)

392(POS)

Creatinine

5
mg/mL

81(NEG)

138(POS)

158(NEG)

259(POS)

230(NEG)

396(POS)

Ethanol

1
%

78(NEG)

136(POS)

151(NEG)

261(POS)

228(NEG)

395(POS)

Glucose

20
mg/mL

81(NEG)

138(POS)

158(NEG)

262(POS)

236(NEG)

403(POS)

Hemoglobin

1
mg/mL

76(NEG)

139(POS)

159(NEG)

261(POS)

228(NEG)

398(POS)

Human serum albumin

5
mg/mL

83(NEG)

140(POS)

165(NEG)

273(POS)

243(NEG)

422(POS)

Oxalic acid

2
mg/mL

74(NEG)

128(POS)

151(NEG)

254(POS)

226(NEG)

388(POS)

Sodium chloride

0.5
M

79(NEG)

139(POS)

159(NEG)

262(POS)

234(NEG)

389(POS)

Urea

6
%

80(NEG)

138(POS)

157(NEG)

261(POS)

233(NEG)

405(POS)

The same experiment was performed in the qualitative mode for each cutoff. All negative and positive samples recovered properly in the presence of the interfering substance.

An additional protocol was executed in which samples containing nordiazepam at control levels (±25 % of cutoff) with specific gravities ranging from 1.006 to 1.034 were tested. As with the other interferences, there were no control cross‑overs on any of the 3 assay cutoffs at either extreme specific gravity level.

For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.

ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on cobas c systems. All special wash programming necessary for avoiding carry‑over is available via the cobas link, manual input is required in certain cases. The latest version of the carry‑over evasion list can be found with the NaOHD/SMS/SmpCln1+2/SCCS Method Sheet and for further instructions refer to the operator’s manual.

Where required, special wash/carry‑over evasion programming must be implemented prior to reporting results with this test.

", "Language": "en" }, { "Name": "OrderInformation", "Value": "

OrderInformation (CC Reagents - cobas + Integra)

Order information

Analyzer(s) on which cobas c pack(s) can be used

06334415190

ONLINE DAT Benzodiazepines II 100 tests

System‑ID 01 6997 5

cobas c 701/702

Materials required (but not provided):

03304671190

Preciset DAT Plus I calibrators CAL 1‑6 (6 x 5 mL)

Codes 431‑436

03304680190

Preciset DAT Plus II calibrators CAL 1‑6 (6 x 5 mL)

Codes 437‑442

03304698190

C.f.a.s. DAT Qualitative Plus (6 x 5 mL)

Code 433

04590856190

C.f.a.s. DAT Qualitative Plus Clinical ( 3 x 5 mL)

Code 699

03312950190

Control Set DAT I (for 300 ng/mL assay)
PreciPos DAT Set I (2 x 10 mL)
PreciNeg DAT Set I (2 x 10 mL)

03312968190

Control Set DAT II (for 100 ng/mL assay)
PreciPos DAT Set II (2 x 10 mL)
PreciNeg DAT Set II (2 x 10 mL)

04500873190

Control Set DAT Clinical (for 100 ng/mL assay)
PreciPos DAT Clinical (2 x 10 mL)
PreciNeg DAT Clinical (2 x 10 mL)

03312976190

Control Set DAT III (for 200 ng/mL assay)
PreciPos DAT Set III (2 x 10 mL)
PreciNeg DAT Set III (2 x 10 mL)

", "Language": "en" }, { "Name": "SystemInformation", "Value": "

System information

BZ1Q2: ACN 8718: for qualitative assay, 100 ng/mL

BZ2Q2: ACN 8719: for qualitative assay, 200 ng/mL

BZ3Q2: ACN 8720: for qualitative assay, 300 ng/mL

BZ1S2: ACN 8728: for semiquantitative assay, 100 ng/mL

BZ2S2: ACN 8729: for semiquantitative assay, 200 ng/mL

BZ3S2: ACN 8730: for semiquantitative assay, 300 ng/mL

BZQ1C: ACN 8727: for qualitative assay, 100 ng/mL;using C.f.a.s. DAT Qualitative Plus Clinical

", "Language": "en" }, { "Name": "Handling", "Value": "

Reagent handling

Ready for use

Carefully invert reagent container several times prior to use to ensure that the reagent components are mixed.

", "Language": "en" }, { "Name": "TestDefinition", "Value": "

Application for urine

Deselect Automatic Rerun for these applications in the Utility menu, Application screen, Range tab.

cobas c 701/702 test definition

Semiquantitative

Qualitative

Assay type

2‑Point End

2‑Point End

Reaction time / Assay points

10 / 10‑26

10 / 10‑26

Wavelength (sub/main)

– /546 nm

– /546 nm

Reaction direction

Increase

Increase

Unit

ng/mL

mAbs

Reagent pipetting

Diluent (H2O)

R1

90 µL

R2

40 µL

Sample volumes

Sample

Sample dilution

100 and 200 ng/mL cutoffs

Sample

Diluent (NaCl)

Normal

4.5 µL

Decreased

4.5 µL

Increased

4.5 µL

300 ng/mL cutoff

Normal

2.0 µL

Decreased

2.0 µL

Increased

2.0 µL

", "Language": "en" }, { "Name": "StorageStability", "Value": "

Storage and stability

Shelf life at 2‑8 °C:

See expiration date on cobas c pack label

On‑board in use and refrigerated on the analyzer:

8 weeks

On‑board on the Reagent Manager:

24 hours

Do not freeze.

", "Language": "en" }, { "Name": "Calibration", "Value": "

Calibration

Calibrators

Semiquantitative applications

100 and 200 ng/mL cutoff assays

S1‑6: Preciset DAT Plus II calibrators, CAL 1‑6

0, 50, 100, 200, 400, 1000 ng/mL

300 ng/mL cutoff assay

S1‑6: Preciset DAT Plus I calibrators, CAL 1‑6

0, 150, 300, 600, 1000, 3000 ng/mL

Qualitative applications

100 ng/mL cutoff assay

S1: Preciset DAT Plus II calibrator - CAL 3 (Test BZ1Q2) , 100 ng/mL, S1: C.f.a.s. DAT Qualitative Plus Clinical (Test BZQ1C) , 100 ng/mL

200 ng/mL cutoff assay

S1: Preciset DAT Plus II calibrator - CAL 4, 200 ng/mL

300 ng/mL cutoff assay

S1: C.f.a.s. DAT Qualitative Plus or Preciset DAT Plus I calibrator - CAL 3, 300 ng/mL

The drug concentrations of the calibrators have been verified by GC‑MS.

Calibration K Factor

For the qualitative applications, enter the K Factor as -1000 into the Calibration menu, Status screen, Calibration Result window.

Calibration mode

Semiquantitative applications

Result Calculation Mode (RCM)

FREFSee Results section

Qualitative applications

Linear

Calibration frequency

Full (semiquantitative) or blank (qualitative) calibration
• after reagent lot change
• as required following quality control procedures

Calibration interval may be extended based on acceptable verification of calibration by the laboratory.

Traceability: This method has been standardized against a primary reference method (GC‑MS).

", "Language": "en" }, { "Name": "Limitations", "Value": "", "Language": "en" }, { "Name": "PerformanceData", "Value": "

Specific performance data

Representative performance data on the analyzers are given below. Results obtained in individual laboratories may differ.

", "Language": "en" }, { "Name": "Precision", "Value": "

Precision

Precision was determined in an internal protocol by running a series of calibrator and controls with repeatability (n = 21) and intermediate precision (n = 40). The following results were obtained:

100 ng/mL cutoff

Semiquantitative precision

Repeatability

Mean

ng/mL

SD

ng/mL

CV

%

Level 1

80

3

3.6

Level 2

98

3

2.9

Level 3

129

3

2.0

Intermediate precision

Mean

ng/mL

SD

ng/mL

CV

%

Level 1

78

3

3.7

Level 2

101

2

2.1

Level 3

124

4

3.1

Qualitative precision

Cutoff (100)

Number tested

Correct results

Confidence level

0.75x

105

105

> 95 % negative reading

1.25x

105

105

> 95 % positive reading

200 ng/mL cutoff

Semiquantitative precision

Repeatability

Mean

ng/mL

SD

ng/mL

CV

%

Level 1

149

3

1.8

Level 2

192

3

1.4

Level 3

247

3

1.3

Intermediate precision

Mean

ng/mL

SD

ng/mL

CV

%

Level 1

145

5

3.7

Level 2

191

5

2.4

Level 3

241

8

3.1

Qualitative precision

Cutoff (200)

Number tested

Correct results

Confidence level

0.75x

105

105

> 95 % negative reading

1.25x

105

105

> 95 % positive reading

300 ng/mL cutoff

Semiquantitative precision

Repeatability

Mean

ng/mL

SD

ng/mL

CV

%

Level 1

227

7

3.1

Level 2

297

8

2.6

Level 3

386

7

1.7

Intermediate precision

Mean

ng/mL

SD

ng/mL

CV

%

Level 1

231

6

2.7

Level 2

301

7

2.3

Level 3

364

8

2.3

Qualitative precision

Cutoff (300)

Number tested

Correct results

Confidence level

0.75x

105

105

> 95 % negative reading

1.25x

105

105

> 95 % positive reading

Results for intermediate precision were obtained on the master system cobas c 501 analyzer.

", "Language": "en" }, { "Name": "MethodComparison", "Value": "", "Language": "en" }, { "Name": "Summary", "Value": "

Summary

The benzodiazepines constitute a class of versatile and widely prescribed central nervous system (CNS) depressant drugs with medically useful anxiolytic, sedative, hypnotic, muscle relaxant, and anticonvulsant activities.

LREFKarch SB, ed. Drug Abuse Handbook. Boca Raton, FL: CRC Press LLC 1998.
,
LREFSalamone SJ, ed. Benzodiazepines and GHB: Detection and Pharmacology. Totowa, NJ: Humana Press 2001.
,
LREFHardman JG, Limbird LE, Gilman A, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw Hill Pub Co. 2001.
,
LREFBaselt RC. Disposition of Toxic Drugs and Chemicals in Man. 7th ed. Foster City, CA: Biomedical Publications 2004.
,
LREFLaurijssens BE, Greenblatt DJ. Pharmacokinetic-pharmacodynamic relationships for benzodiazepines. Clin Pharmacokinet 1996;30:52-76.
The absorption rates, distribution, metabolism, and elimination rates differ significantly among the benzodiazepine derivatives. The quantitative differences in their potencies, pharmacodynamic spectra, and pharmacokinetic properties have led to various therapeutic applications. Clinical distinction of short‑acting versus long‑acting benzodiazepines have been observed in their efficacy, side effect, withdrawal, and dependence potential.
LREFHardman JG, Limbird LE, Gilman A, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw Hill Pub Co. 2001.
,
LREFHallfors DD, Saxe L. The dependence potential of short half-life benzodiazepines: a meta-analysis. Am J Public Health 1993;83:1300-1304.
,
LREFChouinard G. Issues in the clinical use of benzodiazepines: potency, withdrawal, and rebound. J Clin Psychiatry 2004:65(5);7-12.
The extensive and efficacious therapeutic use of the benzodiazepines over the last several decades has inadvertently led to their misuse. Benzodiazepine overdoses are frequently associated with co‑administration of drugs of other classes.
LREFAbernethy DR, Greenblatt DJ, Ochs HR, et al. Benzodiazepine drug-drug interactions commonly occurring in clinical practice. Curr Med Res Opin 1984;8:80-93.
,
LREFTanaka E. Toxicological interactions between alcohol and benzodiazepines. J Toxicol Clin Toxicol 2002;40:69-75.
Acute or chronic alcohol ingestion and benzodiazepines co‑administered may lead to various significant toxicological interactions. The net effect may be influenced by internal, external, and pharmacokinetic factors. Abuse patterns may involve relatively low benzodiazepine doses, as well as high‑dose overuse; therefore, urinary drug/metabolite detection requires the proper selection of a cutoff that suits the requirements of the drug testing program.

Following ingestion, the benzodiazepines of the 1,4‑substituted class (including the triazolobenzodiazepine derivatives) are absorbed, metabolized, and excreted in the urine at different rates as a variety of structurally related metabolites. Metabolite diversity reflects the different physiochemical properties and metabolic pathways of the individual drugs. Overall metabolic similarities include removal of substituents from the β ring of the 1,4‑substituted benzodiazepines, α-hydroxylation of the triazolobenzodiazepines, demethylation, hydroxylation of the three-position carbon of the β ring, and conjugation of hydroxylated metabolites followed by urinary excretion predominantly as glucuronides.

LREFKarch SB, ed. Drug Abuse Handbook. Boca Raton, FL: CRC Press LLC 1998.
,
LREFSalamone SJ, ed. Benzodiazepines and GHB: Detection and Pharmacology. Totowa, NJ: Humana Press 2001.
,
LREFHardman JG, Limbird LE, Gilman A, eds. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 10th ed. New York, NY: McGraw Hill Pub Co. 2001.
,
LREFBaselt RC. Disposition of Toxic Drugs and Chemicals in Man. 7th ed. Foster City, CA: Biomedical Publications 2004.
,
LREFLaurijssens BE, Greenblatt DJ. Pharmacokinetic-pharmacodynamic relationships for benzodiazepines. Clin Pharmacokinet 1996;30:52-76.
The enzymatic hydrolysis of glucuronidated benzodiazepines can increase their cross-reactivities to benzodiazepine immunoassays.
LREFDou C, Bournique JS, Zinda MK, et al. Comparison of the Rates of Hydrolysis of Lorazepam-Glucuronide, Oxazepam-Glucuronide and Temazepam-Glucuronide Catalyzed by E. Coli β-D-Glucuronidase Using the OnLine Benzodiazepine Screening Immunoassay on the Roche/Hitachi 917 Analyzer. J of Forensic Science 2001;46(2):335-340.
,
LREFBeck O, Lin Z, Brodin K, et al. The online screening technique for urinary benzodiazepines: comparison with EMIT, FPIA, and GC-MS. J Anal Toxicology 1997;21(7):554-557.
,
LREFSalamone SJ, Honasoge S, Brenner C, et al. Flunitrazepam excretion patterns using the Abuscreen OnTrak and OnLine immunoassays: comparison with GC-MS. J Anal Toxicol 1997;21:341-345.
,
LREFKlette KL, Wiegand RF, Horn CK, et al. Urine benzodiazepine screening using Roche Online KIMS immunoassay with beta-glucuronidase hydrolysis and confirmation by gas chromatography-mass spectrometry. J Anal Toxicol 2005;29:193-200.
,
LREFValentine JL, Middleton R, Sparks C. Identification of urinary benzodiazepines and their metabolites: comparison of automated HPLC and GC-MS after immunoassay screening of clinical specimens. J Anal Toxicol 1996;20(6):416-424.

", "Language": "en" }, { "Name": "Reagents", "Value": "

Reagents - working solutions

R1

Benzodiazepines antibody (sheep polyclonal); buffer; β‑glucuronidase enzyme; bovine serum albumin (BSA); 0.09 % sodium azide

R2

Conjugated benzodiazepine derivative microparticles; buffer; 0.09 % sodium azide

R1 is in position B and R2 is in position C.

", "Language": "en" }, { "Name": "PrecautionsWarnings", "Value": "

Precautions and warnings

For in vitro diagnostic use for health care professionals. Exercise the normal precautions required for handling all laboratory reagents.

Infectious or microbial waste:
Warning: handle waste as potentially biohazardous material. Dispose of waste according to accepted laboratory instructions and procedures.

Environmental hazards:
Apply all relevant local disposal regulations to determine the safe disposal.

Safety data sheet available for professional user on request.

", "Language": "en" }, { "Name": "Caution", "Value": "", "Language": "en" }, { "Name": "QualityControl", "Value": "

Quality control

For quality control, use control materials as listed in the \"Order information\" section.

In addition, other suitable control material can be used.

Drug concentrations of the controls have been verified by GC‑MS.

The control intervals and limits should be adapted to each laboratory’s individual requirements. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.

Follow the applicable government regulations and local guidelines for quality control.

", "Language": "en" }, { "Name": "SpecimenPreparation", "Value": "

Specimen collection and preparation

Only the specimens listed below were tested and found acceptable.

Urine: Collect urine samples in clean glass or plastic containers. Fresh urine specimens do not require any special handling or pretreatment, but an effort should be made to keep pipetted samples free of gross debris. Samples should be within the normal physiological pH range of 5‑8. No additives or preservatives are required. It is recommended that urine specimens be stored at 2‑8 °C and tested within 5 days of collection.

LREFToxicology and Drug Testing in the Clinical Laboratory; Approved Guideline. 2nd ed. (C52-A2). Clinical and Laboratory Standards Institute 2007;27:33.

For prolonged storage, freezing of the sample is recommended.

Centrifuge highly turbid specimens before testing.

Adulteration or dilution of the sample can cause erroneous results. If adulteration is suspected, another sample should be collected. Specimen validity testing is required for specimens collected under the Mandatory Guidelines for Federal Workplace Drug Testing Programs.

LREFMandatory Guidelines for Federal Workplace Drug Testing Programs. Fed Regist 2008 Nov 25;73:71858-71907.

Specimens containing human‑sourced materials should be handled as if potentially infectious using safe laboratory procedures such as those outlined in Biosafety in Microbiological and Biomedical Laboratories (HHS Publication Number [CDC] 93‑8395).

CAUTION: Specimen dilutions should only be used to interpret results of Calc.? and Samp.? alarms, or when estimating concentration in preparation for GC‑MS or LC‑MS/MS. Dilution results are not intended for patient values. Dilution procedures, when used, should be validated.

", "Language": "en" } ] } } ] }

BNZ2

ONLINE DAT Benzodiazepines II

IVD For in vitro diagnostic use.
BNZ2

Overview

Detailed Specifications

Ordering Information

Compatible Instruments

...
    ...

    Technical Documents

    Access Material Data Sheets, Certificates of Analysis, and other product documentation.

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