In vitro test for the quantitative determination of quinidine in serum and plasma on Roche/Hitachi cobas c systems.
Kinetic interaction of microparticles in solution (KIMS) as measured by changes in light transmission.
The assay is a homogeneous immunoassay based on the principle of measuring changes in scattered light or absorbance which result when activated microparticles aggregate. The microparticles are coated with quinidine and rapidly aggregate in the presence of a quinidine antibody solution. When a sample containing quinidine is introduced, the aggregation reaction is partially inhibited, slowing the rate of the aggregation process. Antibody bound to sample drug is no longer available to promote microparticle aggregation, and subsequent particle lattice formation is inhibited. Thus, a classic inhibition curve with respect to quinidine concentration is obtained, with the maximum rate of aggregation at the lowest quinidine concentration. By monitoring the change in scattered light or absorbance, a concentration-dependent curve is obtained.
0.11‑8 µg/mL (0.34‑24.6 µmol/L)
Manually dilute samples above the measuring range 1 + 1 with the Preciset TDM II Diluent (0 µg/mL) and reassay. Multiply the result by 2 to obtain the specimen value.
Limit of Blank, Limit of Detection and Limit of Quantitation
Limit of Blank | = 0.11 µg/mL (0.34 µmol/L) |
Limit of Detection | = 0.11 µg/mL (0.34 µmol/L) |
Limit of Quantitation | = 0.30 µg/mL (0.92 µmol/L) |
The Limit of Blank, Limit of Detection and Limit of Quantitation were determined in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP17‑A2 requirements.
The Limit of Blank is the 95th percentile value from n ≥ 60 measurements of analyte‑free samples over several independent series. The Limit of Blank corresponds to the concentration below which analyte‑free samples are found with a probability of 95 %.
The Limit of Detection is determined based on the Limit of Blank and the standard deviation of low concentration samples.
The Limit of Detection corresponds to the lowest analyte concentration which can be detected (value above the Limit of Blank with a probability of 95 %).
The Limit of Quantitation is the lowest analyte concentration that can be reproducibly measured with a total error of 20 %. It has been determined using low concentration quinidine samples.
Quinidine is approximately 75 % bound to serum protein.
Serum quinidine levels of 1.5 to 5 µg/mL (4.6 to 15.4 µmol/L*) have been reported as therapeutic, based on nonspecific methodologies that measure quinidine metabolites as well as quinidine.
The therapeutic range using newer, more specific assays has not been established. However, effective reduction of premature ventricular contractions has been reported with blood levels less than 1.0 µg/mL (3.1 µmol/L*).
Toxicity has been reported at a level of 6 µg/mL (18.5 µmol/L*).
* calculated by conversion factor
Toxic side effects include ventricular tachycardia, heart block, thrombocytopenia and “cinchonism”, a group of symptoms including headache, dizziness, tinnitus, nervousness, blurred vision, nausea, and vomiting. Measured quinidine levels are lower using specific methods (HPLC and immunoassays). Clinicians requesting serum quinidine determinations should ask that the method of analysis be specified.
Metabolites of quinidine which may be found in serum are 3(S)‑hydroxyquinidine, 2'‑oxoquinidinone, quinidine‑N-oxide, o‑desmethylquinidine, and the quinidine 10,11‑dihydrodiols. Most of these have been shown to have pharmacological activity in human or animal studies, and some quinidine metabolites may be as potent as the parent drug.
Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.
Criterion: Recovery within ± 10 % of initial value at quinidine levels of approximately 2 and 5 µg/mL (6.2 and 15.4 µmol/L).
Serum/Plasma
Icterus:
Hemolysis:
Lipemia (Intralipid):
Triglycerides: No significant interference from triglycerides up to a concentration of 600 mg/dL.
Rheumatoid factors: No significant interference from rheumatoid factors up to a concentration of 100 IU/mL.
Criterion: Recovery within ± 10 % of initial value at quinidine levels of approximately 2 µg/mL (6.2 µmol/L).
Total protein: No significant interference from total protein in the concentration range of 2‑10 g/dL.
In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.
For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.
A test result flagged with \">Kin3\" indicates unusual reaction kinetics.
Sample dilution, as described for samples above the measuring range, avoids this non‑specific reaction.
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
|
| Analyzer(s) on which cobas c pack(s) can be used | |
ONLINE TDM Quinidine (100 tests) | System‑ID 2103 001 | cobas c 303, cobas c 503 |
Materials required (but not provided):
03375781190 |
| Codes 20743-20748 | |
04521536190 | TDM Control Set |
|
QUIN2: ACN 21030
Ready for use
Mix reagents by gentle inversion numerous times before placing on‑board the analyzer.
Reporting time | 10 min | ||
Wavelength (sub/main) | – /600 nm | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 84 µL | – | |
R2 | - | – | |
R3 | 25 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 1.0 µL | – | – |
Decreased | 1.0 µL | – | – |
Increased | 1.0 µL | – | – |
For further information about the assay test definitions refer to the application parameters setting screen of the corresponding analyzer and assay.
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. |
Calibrators | S1‑6: Preciset TDM II Calibrators |
Calibration mode | Non‑linear |
Calibration frequency | Full calibration |
Calibration interval may be extended based on acceptable verification of calibration by the laboratory.
Traceability: This method has been standardized against USP reference standards.
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.
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).
Repeatability | Mean | SD | CV |
TDMC1a) | 1.07 | 0.0167 | 1.6 |
TDMC2b) | 3.07 | 0.0412 | 1.3 |
TDMC3c) | 4.75 | 0.0537 | 1.1 |
Human serum 1 | 0.232 | 0.0128 | 5.5 |
Human serum 2 | 3.11 | 0.0377 | 1.2 |
Human serum 3 | 4.04 | 0.0396 | 1.0 |
Human serum 4 | 4.91 | 0.0801 | 1.6 |
Human serum 5 | 7.25 | 0.155 | 2.1 |
Intermediate precision | Mean | SD | CV |
TDMC1 FREFTDM Control Set Level I | 1.07 | 0.0361 | 3.4 |
TDMC2 FREFTDM Control Set Level II | 3.16 | 0.0571 | 1.8 |
TDMC3 FREFTDM Control Set Level III | 4.88 | 0.0765 | 1.6 |
Human serum 1 | 0.251 | 0.0330 | 13.2 |
Human serum 2 | 3.11 | 0.0613 | 2.0 |
Human serum 3 | 3.94 | 0.0610 | 1.5 |
Human serum 4 | 4.91 | 0.0995 | 2.0 |
Human serum 5 | 7.25 | 0.162 | 2.2 |
Serum/plasma
Quinidine values for human serum and plasma samples obtained on a cobas c 503 analyzer (y) were compared with those determined using the corresponding reagent on a cobas c 501 analyzer (x).
Sample size (n) = 75 | |
Passing/Bablok LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790. | Linear regression |
y = 1.072x - 0.0813 µg/mL | y = 1.070x - 0.0781 µg/mL |
τ = 0.970 | r = 0.998 |
The sample concentrations were between 0.110 and 7.32 µg/mL. |
Sample size (n) = 74 | |
Passing/Bablok LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790. | Linear regression |
y = 1.023x - 0.00365 µg/mL | y = 1.017x - 0.0349 µg/mL |
τ = 0.958 | r = 0.997 |
The sample concentrations were between 0.190 and 7.38 µg/mL. |
Quinidine is used for the prevention and treatment of ventricular arrhythmias, junctional (nodal) arrhythmias, and supraventricular (atrial) arrhythmias. The quinidine dosage required to achieve therapeutic serum levels is dependent on the drug formulation, patient age, and individual variability in absorption and metabolism.
R1 | Anti-quinidine antibody (mouse monoclonal) and human-sourced material in buffer with preservative |
R3 | Conjugated quinidine derivative microparticles, human-sourced material, and preservative |
R1 is in position B and R3 is in position C.
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.
All human material should be considered potentially infectious. All products derived from human blood are prepared exclusively from the blood of donors tested individually and shown to be free from HBsAg and antibodies to HCV and HIV. The testing methods use assays that have been approved by the FDA or
However, as no testing method can rule out the potential risk of infection with absolute certainty, the material should be handled with the same level of care as a patient specimen. In the event of exposure, the directives of the responsible health authorities should be followed.
This kit contains components classified as follows in accordance with the Regulation (EC) No. 1272/2008:
![](\"http://pim-media.roche.com/Images/GHS_exclam_922241547_All.jpg\"/)
H319 | Causes serious eye irritation. |
Prevention:
P264 | Wash skin thoroughly after handling. |
P280 | Wear eye protection/ face protection. |
Response:
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P337 + P313 | If eye irritation persists: Get medical advice/attention. |
Product safety labeling follows EU GHS guidance.
Contact phone: 1-800-428-2336
For quality control, use control materials as listed in the \"Order information\" section.
In addition, other suitable control material can be used.
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.
For specimen collection and preparation only use suitable tubes or collection containers.
Only the specimens listed below were tested and found acceptable.
Serum: Collect serum using standard sampling tubes.
Plasma: K2‑ or K3‑EDTA, or sodium or lithium heparinized plasma.
Stability: | 8 hours capped at 15‑25 °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.
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.
Do not induce foaming of specimens. Specimens should not be repeatedly frozen and thawed.
Invert thawed specimens several times prior to testing.
In vitro test for the quantitative determination of quinidine in serum and plasma on Roche/Hitachi cobas c systems.
Kinetic interaction of microparticles in solution (KIMS) as measured by changes in light transmission.
The assay is a homogeneous immunoassay based on the principle of measuring changes in scattered light or absorbance which result when activated microparticles aggregate. The microparticles are coated with quinidine and rapidly aggregate in the presence of a quinidine antibody solution. When a sample containing quinidine is introduced, the aggregation reaction is partially inhibited, slowing the rate of the aggregation process. Antibody bound to sample drug is no longer available to promote microparticle aggregation, and subsequent particle lattice formation is inhibited. Thus, a classic inhibition curve with respect to quinidine concentration is obtained, with the maximum rate of aggregation at the lowest quinidine concentration. By monitoring the change in scattered light or absorbance, a concentration-dependent curve is obtained.
0.11‑8 µg/mL (0.34‑24.6 µmol/L)
Manually dilute samples above the measuring range 1 + 1 with the Preciset TDM II Diluent (0 µg/mL) and reassay. Multiply the result by 2 to obtain the specimen value.
Limit of Blank, Limit of Detection and Limit of Quantitation
Limit of Blank | = 0.11 µg/mL (0.34 µmol/L) |
Limit of Detection | = 0.11 µg/mL (0.34 µmol/L) |
Limit of Quantitation | = 0.30 µg/mL (0.92 µmol/L) |
The Limit of Blank, Limit of Detection and Limit of Quantitation were determined in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP17‑A2 requirements.
The Limit of Blank is the 95th percentile value from n ≥ 60 measurements of analyte‑free samples over several independent series. The Limit of Blank corresponds to the concentration below which analyte‑free samples are found with a probability of 95 %.
The Limit of Detection is determined based on the Limit of Blank and the standard deviation of low concentration samples.
The Limit of Detection corresponds to the lowest analyte concentration which can be detected (value above the Limit of Blank with a probability of 95 %).
The Limit of Quantitation is the lowest analyte concentration that can be reproducibly measured with a total error of 20 %. It has been determined using low concentration quinidine samples.
Quinidine is approximately 75 % bound to serum protein.
Serum quinidine levels of 1.5 to 5 µg/mL
(4.6 to 15.4 µmol/L*)
have been reported as therapeutic, based on nonspecific methodologies that measure quinidine metabolites as well as quinidine.
The therapeutic range using newer, more specific assays has not been established. However, effective reduction of premature ventricular contractions has been reported with blood levels less than 1.0 µg/mL
(3.1 µmol/L*).
Toxicity has been reported at a level of 6 µg/mL
(18.5 µmol/L*).
* calculated by conversion factor
Toxic side effects include ventricular tachycardia, heart block, thrombocytopenia and “cinchonism”, a group of symptoms including headache, dizziness, tinnitus, nervousness, blurred vision, nausea, and vomiting. Measured quinidine levels are lower using specific methods (HPLC and immunoassays). Clinicians requesting serum quinidine determinations should ask that the method of analysis be specified.
Metabolites of quinidine which may be found in serum are 3(S)‑hydroxyquinidine, 2'‑oxoquinidinone, quinidine‑N-oxide, o‑desmethylquinidine, and the quinidine 10,11‑dihydrodiols. Most of these have been shown to have pharmacological activity in human or animal studies, and some quinidine metabolites may be as potent as the parent drug.
Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.
Criterion: Recovery within ± 10 % of initial value at quinidine levels of approximately 2 and 5 µg/mL (6.2 and 15.4 µmol/L).
Serum/Plasma
Icterus:
Hemolysis:
Lipemia (Intralipid):
Triglycerides: No significant interference from triglycerides up to a concentration of 600 mg/dL.
Rheumatoid factors: No significant interference from rheumatoid factors up to a concentration of 100 IU/mL.
Criterion: Recovery within ± 10 % of initial value at quinidine levels of approximately 2 µg/mL (6.2 µmol/L).
Total protein: No significant interference from total protein in the concentration range of 2‑10 g/dL.
In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.
For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.
A test result flagged with \">Kin3\" indicates unusual reaction kinetics.
Sample dilution, as described for samples above the measuring range, avoids this non‑specific reaction.
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.
|
| Analyzer(s) on which cobas c pack(s) can be used | |
08252670190 | ONLINE TDM Quinidine (100 tests) | System‑ID 2103 001 |
Materials required (but not provided):
03375781190 | Preciset TDM II Calibrators | Codes 20743-20748 | |
04521536190 | TDM Control Set | Code 20310 Code 20311 Code 20312 |
QUIN2: ACN 21030
Ready for use
Mix reagents by gentle inversion numerous times before placing on‑board the analyzer.
Reporting time | 10 min | ||
Wavelength (sub/main) | – /600 nm | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 84 µL | – | |
R2 | - | – | |
R3 | 25 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 1.0 µL | – | – |
Decreased | 1.0 µL | – | – |
Increased | 1.0 µL | – | – |
For further information about the assay test definitions refer to the application parameters setting screen of the corresponding analyzer and assay.
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. |
Calibrators | S1‑6: Preciset TDM II Calibrators |
Calibration mode | Non‑linear |
Calibration frequency | Full calibration |
Calibration interval may be extended based on acceptable verification of calibration by the laboratory.
Traceability: This method has been standardized against USP reference standards.
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.
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).
Repeatability | Mean | SD | CV |
TDMC1a) | 1.07 | 0.0167 | 1.6 |
TDMC2b) | 3.07 | 0.0412 | 1.3 |
TDMC3c) | 4.75 | 0.0537 | 1.1 |
Human serum 1 | 0.232 | 0.0128 | 5.5 |
Human serum 2 | 3.11 | 0.0377 | 1.2 |
Human serum 3 | 4.04 | 0.0396 | 1.0 |
Human serum 4 | 4.91 | 0.0801 | 1.6 |
Human serum 5 | 7.25 | 0.155 | 2.1 |
Intermediate precision | Mean | SD | CV |
TDMC1 FREFTDM Control Set Level I | 1.07 | 0.0361 | 3.4 |
TDMC2 FREFTDM Control Set Level II | 3.16 | 0.0571 | 1.8 |
TDMC3 FREFTDM Control Set Level III | 4.88 | 0.0765 | 1.6 |
Human serum 1 | 0.251 | 0.0330 | 13.2 |
Human serum 2 | 3.11 | 0.0613 | 2.0 |
Human serum 3 | 3.94 | 0.0610 | 1.5 |
Human serum 4 | 4.91 | 0.0995 | 2.0 |
Human serum 5 | 7.25 | 0.162 | 2.2 |
Serum/plasma
Quinidine values for human serum and plasma samples obtained on a cobas c 503 analyzer (y) were compared with those determined using the corresponding reagent on a cobas c 501 analyzer (x).
Sample size (n) = 75 | |
Passing/Bablok LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790. | Linear regression |
y = 1.072x - 0.0813 µg/mL | y = 1.070x - 0.0781 µg/mL |
τ = 0.970 | r = 0.998 |
The sample concentrations were between 0.110 and 7.32 µg/mL. |
Sample size (n) = 74 | |
Passing/Bablok LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790. | Linear regression |
y = 1.023x - 0.00365 µg/mL | y = 1.017x - 0.0349 µg/mL |
τ = 0.958 | r = 0.997 |
The sample concentrations were between 0.190 and 7.38 µg/mL. |
Quinidine is used for the prevention and treatment of ventricular arrhythmias, junctional (nodal) arrhythmias, and supraventricular (atrial) arrhythmias. The quinidine dosage required to achieve therapeutic serum levels is dependent on the drug formulation, patient age, and individual variability in absorption and metabolism.
R1 | Anti-quinidine antibody (mouse monoclonal) and human-sourced material in buffer with preservative |
R3 | Conjugated quinidine derivative microparticles, human-sourced material, and preservative |
R1 is in position B and R3 is in position C.
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.
| |
Warning |
H319 | Causes serious eye irritation. |
Prevention:
P264 | Wash skin thoroughly after handling. |
P280 | Wear eye protection/ face protection. |
Response:
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P337 + P313 | If eye irritation persists: Get medical advice/attention. |
Product safety labeling follows EU GHS guidance.
Contact phone: all countries: +49-621-7590
All human material should be considered potentially infectious. All products derived from human blood are prepared exclusively from the blood of donors tested individually and shown to be free from HBsAg and antibodies to HCV and HIV. The testing methods use assays that have been approved by the FDA or that are in compliance with the legal rules applicable to placing in vitro diagnostic medical devices for human use on the market in the European Union.
However, as no testing method can rule out the potential risk of infection with absolute certainty, the material should be handled with the same level of care as a patient specimen. In the event of exposure, the directives of the responsible health authorities should be followed.
For quality control, use control materials as listed in the “Order information” section. In addition, other suitable control material can be used.
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.
For specimen collection and preparation only use suitable tubes or collection containers.
Only the specimens listed below were tested and found acceptable.
Serum: Collect serum using standard sampling tubes.
Plasma: K2‑ or K3‑EDTA, or sodium or lithium heparinized plasma.
Stability: | 8 hours capped at 15‑25 °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.
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.
Do not induce foaming of specimens. Specimens should not be repeatedly frozen and thawed.
Invert thawed specimens several times prior to testing.
In vitro test for the quantitative determination of quinidine in serum and plasma on Roche/Hitachi cobas c systems.
Kinetic interaction of microparticles in solution (KIMS) as measured by changes in light transmission.
The assay is a homogeneous immunoassay based on the principle of measuring changes in scattered light or absorbance which result when activated microparticles aggregate. The microparticles are coated with quinidine and rapidly aggregate in the presence of a quinidine antibody solution. When a sample containing quinidine is introduced, the aggregation reaction is partially inhibited, slowing the rate of the aggregation process. Antibody bound to sample drug is no longer available to promote microparticle aggregation, and subsequent particle lattice formation is inhibited. Thus, a classic inhibition curve with respect to quinidine concentration is obtained, with the maximum rate of aggregation at the lowest quinidine concentration. By monitoring the change in scattered light or absorbance, a concentration-dependent curve is obtained.
0.11‑8 µg/mL (0.34‑24.6 µmol/L)
Manually dilute samples above the measuring range 1 + 1 with the Preciset TDM II Diluent (0 µg/mL) and reassay. Multiply the result by 2 to obtain the specimen value.
Limit of Blank, Limit of Detection and Limit of Quantitation
Limit of Blank | = 0.11 µg/mL (0.34 µmol/L) |
Limit of Detection | = 0.11 µg/mL (0.34 µmol/L) |
Limit of Quantitation | = 0.30 µg/mL (0.92 µmol/L) |
The Limit of Blank, Limit of Detection and Limit of Quantitation were determined in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP17‑A2 requirements.
The Limit of Blank is the 95th percentile value from n ≥ 60 measurements of analyte‑free samples over several independent series. The Limit of Blank corresponds to the concentration below which analyte‑free samples are found with a probability of 95 %.
The Limit of Detection is determined based on the Limit of Blank and the standard deviation of low concentration samples.
The Limit of Detection corresponds to the lowest analyte concentration which can be detected (value above the Limit of Blank with a probability of 95 %).
The Limit of Quantitation is the lowest analyte concentration that can be reproducibly measured with a total error of 20 %. It has been determined using low concentration quinidine samples.
Quinidine is approximately 75 % bound to serum protein.
Serum quinidine levels of 1.5 to 5 µg/mL
(4.6 to 15.4 µmol/L*)
have been reported as therapeutic, based on nonspecific methodologies that measure quinidine metabolites as well as quinidine.
The therapeutic range using newer, more specific assays has not been established. However, effective reduction of premature ventricular contractions has been reported with blood levels less than 1.0 µg/mL
(3.1 µmol/L*).
Toxicity has been reported at a level of 6 µg/mL
(18.5 µmol/L*).
* calculated by conversion factor
Toxic side effects include ventricular tachycardia, heart block, thrombocytopenia and “cinchonism”, a group of symptoms including headache, dizziness, tinnitus, nervousness, blurred vision, nausea, and vomiting. Measured quinidine levels are lower using specific methods (HPLC and immunoassays). Clinicians requesting serum quinidine determinations should ask that the method of analysis be specified.
Metabolites of quinidine which may be found in serum are 3(S)‑hydroxyquinidine, 2'‑oxoquinidinone, quinidine‑N-oxide, o‑desmethylquinidine, and the quinidine 10,11‑dihydrodiols. Most of these have been shown to have pharmacological activity in human or animal studies, and some quinidine metabolites may be as potent as the parent drug.
Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.
Criterion: Recovery within ± 10 % of initial value at quinidine levels of approximately 2 and 5 µg/mL (6.2 and 15.4 µmol/L).
Serum/Plasma
Icterus:
Hemolysis:
Lipemia (Intralipid):
Triglycerides: No significant interference from triglycerides up to a concentration of 600 mg/dL.
Rheumatoid factors: No significant interference from rheumatoid factors up to a concentration of 100 IU/mL.
Criterion: Recovery within ± 10 % of initial value at quinidine levels of approximately 2 µg/mL (6.2 µmol/L).
Total protein: No significant interference from total protein in the concentration range of 2‑10 g/dL.
In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.
For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.
A test result flagged with \">Kin3\" indicates unusual reaction kinetics.
Sample dilution, as described for samples above the measuring range, avoids this non‑specific reaction.
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.
|
| Analyzer(s) on which cobas c pack(s) can be used | |
08252670190 | ONLINE TDM Quinidine (100 tests) | System‑ID 2103 001 | cobas c 503 |
03375781190 | Preciset TDM II Calibrators | Codes 20743-20748 | |
04521536190 | TDM Control Set | Code 20310 Code 20311 Code 20312 |
QUIN2: ACN 21030
Ready for use
Mix reagents by gentle inversion numerous times before placing on‑board the analyzer.
Reporting time | 10 min | ||
Wavelength (sub/main) | – /600 nm | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 84 µL | – | |
R2 | - | – | |
R3 | 25 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 1.0 µL | – | – |
Decreased | 1.0 µL | – | – |
Increased | 1.0 µL | – | – |
For further information about the assay test definitions refer to the application parameters setting screen of the corresponding analyzer and assay.
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. |
Calibrators | S1‑6: Preciset TDM II Calibrators |
Calibration mode | Non‑linear |
Calibration frequency | Full calibration |
Calibration interval may be extended based on acceptable verification of calibration by the laboratory.
Traceability: This method has been standardized against USP reference standards.
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.
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:
Repeatability | Mean | SD | CV |
TDMC1a) | 1.07 | 0.0167 | 1.6 |
TDMC2b) | 3.07 | 0.0412 | 1.3 |
TDMC3c) | 4.75 | 0.0537 | 1.1 |
Human serum 1 | 0.232 | 0.0128 | 5.5 |
Human serum 2 | 3.11 | 0.0377 | 1.2 |
Human serum 3 | 4.04 | 0.0396 | 1.0 |
Human serum 4 | 4.91 | 0.0801 | 1.6 |
Human serum 5 | 7.25 | 0.155 | 2.1 |
Intermediate precision | Mean | SD | CV |
TDMC1 FREFTDM Control Set Level I | 1.07 | 0.0361 | 3.4 |
TDMC2 FREFTDM Control Set Level II | 3.16 | 0.0571 | 1.8 |
TDMC3 FREFTDM Control Set Level III | 4.88 | 0.0765 | 1.6 |
Human serum 1 | 0.251 | 0.0330 | 13.2 |
Human serum 2 | 3.11 | 0.0613 | 2.0 |
Human serum 3 | 3.94 | 0.0610 | 1.5 |
Human serum 4 | 4.91 | 0.0995 | 2.0 |
Human serum 5 | 7.25 | 0.162 | 2.2 |
Serum/plasma
Quinidine values for human serum and plasma samples obtained on a cobas c 503 analyzer (y) were compared with those determined using the corresponding reagent on a cobas c 501 analyzer (x).
Sample size (n) = 75 | |
Passing/Bablok LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790. | Linear regression |
y = 1.072x - 0.0813 µg/mL | y = 1.070x - 0.0781 µg/mL |
τ = 0.970 | r = 0.998 |
The sample concentrations were between 0.110 and 7.32 µg/mL. |
Quinidine is used for the prevention and treatment of ventricular arrhythmias, junctional (nodal) arrhythmias, and supraventricular (atrial) arrhythmias. The quinidine dosage required to achieve therapeutic serum levels is dependent on the drug formulation, patient age, and individual variability in absorption and metabolism.
R1 | Anti-quinidine antibody (mouse monoclonal) and human-sourced material in buffer with preservative |
R3 | Conjugated quinidine derivative microparticles, human-sourced material, and preservative |
R1 is in position B and R3 is in position C.
For in vitro diagnostic use.
Exercise the normal precautions required for handling all laboratory reagents.
Disposal of all waste material should be in accordance with local guidelines.
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.
All human material should be considered potentially infectious. All products derived from human blood are prepared exclusively from the blood of donors tested individually and shown to be free from HBsAg and antibodies to HCV and HIV. The testing methods used assays approved by the FDA or cleared in compliance with the European Directive 98/79/EC, Annex II, List A.
However, as no testing method can rule out the potential risk of infection with absolute certainty, the material should be handled with the same level of care as a patient specimen. In the event of exposure, the directives of the responsible health authorities should be followed.
For quality control, use control materials as listed in the “Order information” section. In addition, other suitable control material can be used.
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.
For specimen collection and preparation only use suitable tubes or collection containers.
Only the specimens listed below were tested and found acceptable.
Serum: Collect serum using standard sampling tubes.
Plasma: K2‑ or K3‑EDTA, or sodium or lithium heparinized plasma.
Stability: | 8 hours capped at 15‑25 °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.
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.
Do not induce foaming of specimens. Specimens should not be repeatedly frozen and thawed.
Invert thawed specimens several times prior to testing.
In vitro test for the quantitative determination of quinidine in serum and plasma on Roche/Hitachi cobas c systems.
Kinetic interaction of microparticles in solution (KIMS) as measured by changes in light transmission.
The assay is a homogeneous immunoassay based on the principle of measuring changes in scattered light or absorbance which result when activated microparticles aggregate. The microparticles are coated with quinidine and rapidly aggregate in the presence of a quinidine antibody solution. When a sample containing quinidine is introduced, the aggregation reaction is partially inhibited, slowing the rate of the aggregation process. Antibody bound to sample drug is no longer available to promote microparticle aggregation, and subsequent particle lattice formation is inhibited. Thus, a classic inhibition curve with respect to quinidine concentration is obtained, with the maximum rate of aggregation at the lowest quinidine concentration. By monitoring the change in scattered light or absorbance, a concentration-dependent curve is obtained.
0.11‑8 µg/mL (0.34‑24.6 µmol/L)
Manually dilute samples above the measuring range 1 + 1 with the Preciset TDM II Diluent (0 µg/mL) and reassay. Multiply the result by 2 to obtain the specimen value.
Lower detection limit of the test
0.09 μg/mL (0.28 μmol/L)
The lower detection limit represents the lowest measurable analyte level that can be distinguished from zero. It is calculated as the value lying 2 standard deviations above that of the 0 µg/mL calibrator (standard 1 + 2 SD, repeatability, n = 21).
Quinidine is approximately 75 % bound to serum protein.
Metabolites of quinidine which may be found in serum are 3(S)‑hydroxyquinidine, 2'‑oxoquinidinone, quinidine‑N-oxide, o‑desmethylquinidine, and the quinidine 10,11‑dihydrodiols. Most of these have been shown to have pharmacological activity in human or animal studies, and some quinidine metabolites may be as potent as the parent drug.
Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.
Criterion: Recovery within ± 10 % of initial value at quinidine levels of approximately 2 and 5 µg/mL (6.2 and 15.4 µmol/L).
Serum/Plasma
Icterus:
Hemolysis:
Lipemia (Intralipid):
Criterion: Recovery within ± 10 % of initial value at quinidine levels of approximately 2 µg/mL (6.2 µmol/L).
Total protein: No significant interference from total protein in the concentration range of 2‑10 g/dL.
In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.
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
Where required, special wash/carry‑over evasion programming must be implemented prior to reporting results with this test.
|
| Analyzer(s) on which cobas c pack(s) can be used | |
04490991 190 | ONLINE TDM Quinidine (75 tests) | System‑ID 07 6984 3 | cobas c 311, cobas c 501/502 |
Materials required (but not provided):
03375781 190 | Preciset TDM II Calibrators | Codes 743-748 | |
04521536 190 | TDM Control Set | Code 310 Code 311 Code 312 |
For cobas c 311/501 analyzers:
QUIN2: ACN 437
For cobas c 502 analyzers:
QUIN2: ACN 8437
Ready for use
Mix reagents by gentle inversion numerous times before placing on‑board the analyzer.
Deselect Automatic Rerun for these applications in the Utility menu, Application screen, Range tab.
Assay type | 2‑Point End | ||
Reaction time /Assay points: | 10 / 26‑54 | ||
Wavelength (sub/main) | – /600 nm | ||
Reaction direction | Increase | ||
Unit | µg/mL | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 85 µL | – | |
R2 | 82 µL | – | |
R3 | 50 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 2.0 µL | – | – |
Decreased | 2.0 µL | – | – |
Increased | 2.0 µL | – | – |
Assay type | 2‑Point End | ||
Reaction time /Assay points: | 10 / 40‑66 | ||
Wavelength (sub/main) | – /600 nm | ||
Reaction direction | Increase | ||
Unit | µg/mL | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 85 µL | – | |
R2 | 82 µL | – | |
R3 | 50 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 2.0 µL | – | – |
Decreased | 2.0 µL | – | – |
Increased | 2.0 µL | – | – |
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. |
Calibrators | S1‑6: Preciset TDM II Calibrators |
Calibration mode | RCM |
Calibration frequency | 6‑point calibration |
Calibration interval may be extended based on acceptable verification of calibration by the laboratory.
Traceability: This method has been standardized against USP
Representative performance data on the analyzers are given below. Results obtained in individual laboratories may differ.
Precision was determined using human samples and controls in a modified NCCLS EP5‑A protocol (repeatability n = 63, intermediate precision n = 63). The following results were obtained on a
Repeatability | Mean | SD | CV | ||
|---|---|---|---|---|---|
µg/mL | µmol/L | µg/mL | µmol/L | % | |
Control 1 | 1.04 | 3.20 | 0.02 | 0.06 | 2.2 |
Control 2 | 3.12 | 9.61 | 0.03 | 0.09 | 1.1 |
Control 3 | 5.00 | 15.4 | 0.05 | 0.2 | 1.0 |
HS 1 | 1.87 | 5.76 | 0.03 | 0.09 | 1.5 |
HS 2 | 6.75 | 20.8 | 0.08 | 0.3 | 1.1 |
Intermediate precision | Mean | SD | CV | ||
|---|---|---|---|---|---|
µg/mL | µmol/L | µg/mL | µmol/L | % | |
Control 1 | 1.04 | 3.20 | 0.03 | 0.09 | 3.3 |
Control 2 | 3.12 | 9.61 | 0.05 | 0.15 | 1.7 |
Control 3 | 5.00 | 15.4 | 0.06 | 0.2 | 1.3 |
HS 1 | 1.87 | 5.76 | 0.04 | 0.12 | 2.3 |
HS 2 | 6.75 | 20.8 | 0.09 | 0.3 | 1.3 |
Serum/plasma
Quinidine values for human serum and plasma samples obtained on a
Roche/Hitachi 917 analyzer | Sample size (n) = 74 |
Passing/Bablok LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790. | Linear regression |
y = 0.962x - 0.054 µg/mL | y = 0.969x - 0.061 µg/mL |
τ = 0.959 | r = 0.996 |
The sample concentrations were between 0.5 and 6.8 µg/mL (1.5 and 20.9 µmol/L). |
COBAS INTEGRA 700 analyzer | Sample size (n) = 74 |
Passing/Bablok LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790. | Linear regression |
y = 1.099x - 0.022 µg/mL | y = 1.096x - 0.030 µg/mL |
τ = 0.919 | r = 0.991 |
The sample concentrations were between 0.4 and 5.8 µg/mL (1.2 and 17.9 µmol/L). |
Quinidine is used for the prevention and treatment of ventricular arrhythmias, junctional (nodal) arrhythmias, and supraventricular (atrial) arrhythmias. The quinidine dosage required to achieve therapeutic serum levels is dependent on the drug formulation, patient age, and individual variability in absorption and metabolism.
R1+R2 | Anti-quinidine antibody (mouse monoclonal) and human-sourced material in buffer with preservative |
R3 | Conjugated quinidine derivative microparticles, human-sourced material, and preservative |
R1 is in position A, R2 is in position B and R3 is in position C.
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.
This kit contains components classified as follows in accordance with the Regulation (EC) No. 1272/2008:
| |
Warning |
H319 | Causes serious eye irritation. |
Prevention:
P264 | Wash skin thoroughly after handling. |
P280 | Wear eye protection/ face protection. |
Response:
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. |
P337 + P313 | If eye irritation persists: Get medical advice/attention. |
Product safety labeling follows EU GHS guidance.
Contact phone: all countries: +49-621-7590, USA: 1-800-428-2336
All human material should be considered potentially infectious. All products derived from human blood are prepared exclusively from the blood of donors tested individually and shown to be free from HBsAg and antibodies to HCV and HIV. The testing methods use assays that have been approved by the FDA or that are in compliance with the legal rules applicable to placing in vitro diagnostic medical devices for human use on the market in the European Union.
However, as no testing method can rule out the potential risk of infection with absolute certainty, the material should be handled with the same level of care as a patient specimen. In the event of exposure, the directives of the responsible health authorities should be followed.
For quality control, use control materials as listed in the “Order Information” section. In addition, other suitable control material can be used.
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.
For specimen collection and preparation only use suitable tubes or collection containers.
Only the specimens listed below were tested and found acceptable.
Serum: Collect serum using standard sampling tubes.
Plasma: K2‑ or K3‑EDTA, or sodium or lithium heparinized plasma.
Stability: | 8 hours capped at 15‑25 °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.
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.
Do not induce foaming of specimens. Specimens should not be repeatedly frozen and thawed.
Invert thawed specimens several times prior to testing.
ONLINE TDM Quinidine
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