In vitro test for the quantitative determination of cholinesterase in human serum and plasma on Roche/Hitachi cobas c systems.
CHE | ||
butyrylthiocholine + H2O |
| thiocholine + butyrate |
thiocholine + potassium hexacyanoferrate (III) |
|
dithiobis(choline) + potassium hexacyanoferrate (II) |
Cholinesterase catalyzes the hydrolysis of butyrylthiocholine to thiocholine and butyrate. Thiocholine instantaneously reduces the yellow hexacyanoferrate (III) to the almost colorless hexacyanoferrate (II). This decrease in color can be measured photometrically.
To determine the dibucaine number (DN), cholinesterase activity is measured with and without enzyme inhibitor dibucaine. The dibucaine number is calculated as follows:
DN = 100 – | CHE activity with inhibitor | x 100 |
CHE activity without inhibitor |
CHET2: 100‑14000 U/L (1.67‑234 µkat/L)
CHED2: 250‑7000 U/L (4.18‑117 µkat/L)
Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:2 dilution. Results from samples diluted using the rerun function are automatically multiplied by a factor of 2.
Lower limits of measurement
Lower detection limit of the test:
CHET2: 100 U/L (1.67 µkat/L)
CHED2: 250 U/L (4.18 µkat/L)
The lower detection limit represents the lowest measurable analyte level that can be distinguished from zero. It is calculated as the value lying 3 standard deviations above that of the lowest standard (standard 1 + 3 SD, repeatability, n = 21).
Values below the lower detection limit (< 100 U/L) will not be flagged by the instrument.
Children, men, women (aged 40 years or more): 5320‑12920 U/L (89‑215.3 µkat/L)
Women aged 16‑39 years, not pregnant, not taking hormonal contraceptives: 4260‑11250 U/L (71‑187 µkat/L)
Women aged 18‑41 years, pregnant or taking contraceptives: 3650‑9120 U/L (61‑152 µkat/L)
Dibucaine number
Dibucaine number for the cholinesterase variants U (usual) and A (atypical):
Normal individuals | UU | Dibucaine Number | ≥ 73 |
Heterozygous individuals | UA | Dibucaine Number | 72‑57 |
Homozygous individuals | AA | Dibucaine Number | ≤ 50 |
DN results below 57 should be considered to indicate a potentially high risk of succinyldicholine sensitivity.
Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.
a) Calculated with a temperature conversion factor of 1.52 (25 → 37 °C)
CHET2
Criterion: Recovery within ± 10 % of initial value at a cholinesterase activity of 5000 U/L (83.5 µkat/L).
Icterus:
Hemolysis:
Lipemia (Intralipid):
Drugs: No interference was found at therapeutic concentrations using common drug panels.
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.
CHED2
Criterion: Recovery within ± 10 % of initial value at a cholinesterase activity of 1250 U/L (20.9 µkat/L).
Icterus:
Hemolysis:
Lipemia (Intralipid):
Drugs: No interference was found at therapeutic concentrations using common drug panels.
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 Roche/Hitachi 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.
|
| Analyzer(s) on which cobas c pack(s) can be used | |
05168503 190* | Cholinesterase Gen.2 (650 tests) | System‑ID 05 6842 1 | Roche/Hitachi cobas c 701/702 |
05168503 214* | Cholinesterase Gen.2 (650 tests) | System‑ID 05 6842 1 | Roche/Hitachi cobas c 701/702 |
Materials required (but not provided):
05168511 190 | Dibucaine**(13.5 mL) | System‑ID 03 7458 8 | |
10759350 190 | Calibrator f.a.s. (12 x 3 mL) | Code 401 | |
10759350 360 | Calibrator f.a.s. (12 x 3 mL, for USA) | Code 401 | |
12149435 122 | Precinorm U plus (10 x 3 mL) | Code 300 | |
12149435 160 | Precinorm U plus (10 x 3 mL, for USA) | Code 300 | |
12149443 122 | Precipath U plus (10 x 3 mL) | Code 301 | |
12149443 160 | Precipath U plus (10 x 3 mL, for USA) | Code 301 | |
05117003 190 | PreciControl ClinChem Multi 1 (20 x 5 mL) | Code 391 | |
05947626 190 | PreciControl ClinChem Multi 1 (4 x 5 mL) | Code 391 | |
05947626 160 | PreciControl ClinChem Multi 1 (4 x 5 mL, for USA) | Code 391 | |
05117216 190 | PreciControl ClinChem Multi 2 (20 x 5 mL) | Code 392 | |
05947774 190 | PreciControl ClinChem Multi 2 (4 x 5 mL) | Code 392 | |
05947774 160 | PreciControl ClinChem Multi 2 (4 x 5 mL, for USA) | Code 392 | |
05172152 190 | Diluent NaCl 9 % (119 mL) | System‑ID 08 6869 3 |
* Some kits shown may not be available in all countries.
** The value presented on the instrument inventory screen is around 9 mL to account for the dead volume of the containers. This corresponds to 400 tests.
CHET2: ACN 8534, total cholinesterase
CHED2: ACN 8434, inhibited cholinesterase
Ready for use
cobas c 701/702 test definition | |||
Assay type | Rate A | ||
Reaction time / Assay points | 10 / 25‑31 | ||
Wavelength (sub/main) | 700/415 nm | ||
Reaction direction | Decrease | ||
Units | U/L (µkat/L, kU/L) | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 120 µL | – | |
R3 | 24 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 2 µL | – | – |
Decreased | 10 µL | 15 µL | 135 µL |
Increased | 4 µL | – | – |
cobas c 701/702 test definition | |||
Assay type | Rate A | ||
Reaction time / Assay points | 10 / 25‑31 | ||
Wavelength (sub/main) | 700/415 nm | ||
Reaction direction | Decrease | ||
Units | U/L (µkat/L, kU/L) | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 100 µL | – | |
R2 (Special Reagent) | 20 µL | – | |
R3 | 24 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 2 µL | – | – |
Decreased | 2 µL | – | – |
Increased | 4 µL | – | – |
Calculated test definition for dibucaine number
Abbreviated calculated test name CHE2R
Equation 100 – (CHED2/CHET2) x 100
Use a predefined profile for simultaneous order entry of CHET2, CHED2 and CHE2R tests from the same sample. The ratio for dibucaine number will automatically be calculated after results of both tests are available.
Please refer to Operator Manual, section profile and calculated test.
CHE2 | |
Shelf life at 2‑8 °C: | See expiration date on cobas c pack label. |
On‑board in use and refrigerated on the analyzer: | 4 weeks |
On‑board on the Reagent Manager: | 24 hours |
DIBU | |
Shelf life at 2‑8 °C: | See expiration date on cobas c pack label. |
On‑board in use and refrigerated on the analyzer: | 4 weeks |
On‑board on the Reagent Manager: | 24 hours |
Diluent NaCl 9 % | |
Shelf life at 2‑8 °C: | See expiration date on cobas c pack label. |
On‑board in use and refrigerated on the analyzer: | 4 weeks |
On‑board on the Reagent Manager: | 24 hours |
Calibrators | S1: H2O |
Calibration mode | Linear |
Calibration frequency | 2‑point calibration |
Calibration interval may be extended based on acceptable verification of calibration by the laboratory.
Traceability: This test has been standardized against a reference method using a manual application of the butyrylthiocholine/hexacyanoferrate (IlI) method on a manual photometer and the published molar absorptivity ε of hexacyanoferrate (III).
Calibrator | Transfer of blank and k‑factor from CHET2 |
Calibration frequency | - update of blank and k‑factor after each CHET2 calibration |
Note:For the very first calibration of CHET2 set CHED2 inactive. After completion of the CHET2-calibration, set CHED2 again to active and transfer the blank and k‑factor to CHED2.
For further measurements only CHET2 has to be calibrated with calibrator C.f.a.s. and H2O. For CHED2 calibration always use the blank and calibration factor obtained in the CHET2 calibration.
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 an internal protocol with repeatability (n = 21) and intermediate precision (3 aliquots per run, 1 run per day, 21 days). The following results were obtained:
Repeatability | Mean | SD | CV |
Precinorm U | 3118 (52.1) | 19 (0.3) | 0.6 |
Precipath U | 4912 (82.0) | 25 (0.4) | 0.5 |
Human serum A | 3047 (50.9) | 27 (0.5) | 0.9 |
Human serum B | 5422 (90.5) | 23 (0.4) | 0.4 |
Human serum C | 11785 (197) | 50 (1) | 0.4 |
Intermediate precision | Mean | SD | CV |
Precinorm U | 4707 (78.6) | 49 (0.82) | 1.0 |
Precipath U | 4838 (80.8) | 45 (0.75) | 0.9 |
Human serum 3 | 1002 (16.7) | 26 (0.43) | 2.6 |
Human serum 4 | 6683 (112) | 74 (1.24) | 1.1 |
Results for intermediate precision were obtained on the master system cobas c 501 analyzer.
CHET2
Cholinesterase values for human serum and plasma samples obtained on a Roche/Hitachi cobas c 701 analyzer (y) were compared with those determined using the corresponding reagent on Roche/Hitachi cobas c 501 analyzer (x).
Sample size (n) = 83
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 = 0.989x + 24.4 U/L | y = 0.987x + 29.0 U/L |
τ = 0.973 | r = 0.999 |
The sample activities were between 1693 and 13586 U/L (28.3 and 227 µkat/L). |
CHED2
Total and inhibited cholinesterase values, CHET2 (x) and CHED2 (y), for human serum and plasma samples obtained on a Roche/Hitachi cobas c 701 analyzer were compared.
Sample size (n) = 84
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 = 0.275x - 127 U/L | y = 0.273x - 102 U/L |
τ = 0.954 | r = 0.997 |
The sample activities were between 1699 and 13832 U/L (28.4 and 231 µkat/L). |
Cholinesterase (pseudocholinesterase or cholinesterase II) is found in the liver, pancreas, heart, serum and in the white matter of the brain. This enzyme must not be confused with acetylcholinesterase from erythrocytes (EC 3.1.1.7), which is also referred to as cholinesterase I.
The biological function of cholinesterase is unknown. Serum cholinesterase serves as an indicator of possible insecticide poisoning. It is measured as an index of liver function. In preoperative screening, cholinesterase is used to detect patients with atypical forms of the enzyme and hence avoid prolonged apnea caused by slow elimination of muscle relaxants.
At least 6 different genetic variants of serum cholinesterase have been described (A, F, J, K, S and U). The normal most common phenotype is designated U. The atypical forms A, F and S are described by high resistance to dibucaine inhibition (A), increased resistance to fluoride inhibition (F), and absence of catalytic activity (S). The homozygous forms AA or FF are found in only 0.3 to 0.5 % of the caucasian population. The genotypes most susceptible to prolonged anesthesia and/or apnea after succinyldicholine administration are AA, AS, and SS (severe risk); AF, FS, and FF (moderate risk); and to some extent, UA (usually only during pregnancy). In such cases succinyldicholine anesthesia should be avoided. Measurements of total serum cholinesterase activity as well as determination of dibucaine number and fluoride number are needed to characterize cholinesterase variants fully. The dibucaine number indicates the percentage inhibition of enzyme activity in the presence of a standard concentration of dibucaine.
Depressed cholinesterase levels are found in cases of intoxication with organophosphorus compounds and in hepatitis, cirrhosis, myocardial infarction, acute infections and atypical phenotypes of the enzyme. This assay is based on the method published by Schmidt et al.
R1 | Pyrophosphate buffer: 92 mmol/L, pH 7.7; potassium hexacyanoferrate (III): 2.4 mmol/L |
R3 | GOOD's buffer: 10 mmol/L, pH 4.0; butyrylthiocholine: 46 mmol/L; stabilizers |
Dibucaine (for ACN 8434) | |
R2 | Dibucaine: 2.6 mmol/L, pH 6.3 |
(Special Reagent) |
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.
CHET2
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.
Plasma: Li‑heparin and K2‑EDTA plasma.
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.
Stability: LREFTietz NW, ed. Clinical Guide to Laboratory Tests, 3rd ed. Philadelphia PA: WB Saunders Company 1995;132-133. ,LREFUse of Anticoagulants in Diagnostic Laboratory Investigations. WHO Publication WHO/DIL/LAB/99.1 Rev. 2: Jan 2002. ,LREFHuizenga JR, van der Belt K, Gips CH. The Effect of Storage at Different Temperatures on Cholinesterase Activity in Human Serum. J Clin Chem Clin Biochem 1985;24:283-385. | 6 hours at 15‑25 °C |
In vitro test for the quantitative determination of cholinesterase in human serum and plasma on Roche/Hitachi cobas c systems.
butyrylthiocholine + H2O | CHE | thiocholine + butyrate |
thiocholine + potassium hexacyanoferrate (III) | |
dithiobis(choline) + potassium hexacyanoferrate (II) |
Cholinesterase catalyzes the hydrolysis of butyrylthiocholine to thiocholine and butyrate. Thiocholine instantaneously reduces the yellow hexacyanoferrate (III) to the almost colorless hexacyanoferrate (II). This decrease in color can be measured photometrically.
100‑14000 U/L (1.67‑234 µkat/L)
Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:2 dilution. Results from samples diluted using the rerun function are automatically multiplied by a factor of 2.
Limit of Blank, Limit of Detection and Limit of Quantitation
Limit of Blank | = 100 U/L (1.67 µkat/L) |
Limit of Detection | = 100 U/L (1.67 µkat/L) |
Limit of Quantitation | = 100 U/L (1.67 µkat/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 activity 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 activity samples.
The Limit of Detection corresponds to the lowest analyte activity which can be detected (value above the Limit of Blank with a probability of 95 %).
The Limit of Quantitation is the lowest analyte activity that can be reproducibly measured with a total error of 20 %. It has been determined using low activity cholinesterase samples.
Calculated with a temperature conversion factor of 1.52 (25 → 37 °C)
Children, men, women (aged 40 years or more): 5320‑12920 U/L
Women aged 16‑39 years, not pregnant, not taking hormonal contraceptives: 4260‑11250 U/L
Women aged 18‑41 years, pregnant or taking contraceptives: 3650‑9120 U/L
Children, men, women (aged 40 years or more): 89‑215 µkat/L
Women aged 16‑39 years, not pregnant, not taking hormonal contraceptives: 71‑187 µkat/L
Women aged 18‑41 years, pregnant or taking contraceptives: 61‑152 µkat/L
*calculated by unit conversion factor
Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.
Roche has not evaluated reference ranges in a pediatric population.
Criterion: Recovery within ± 10 % of initial value at a cholinesterase activity of 5000 U/L.
Icterus:
Hemolysis:
Lipemia (Intralipid):
Drugs: No interference was found at therapeutic concentrations using common drug panels.
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 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 | |
08105561190 | Cholinesterase Gen.2 (1050 tests) | System‑ID 2037 001 | |
10759350360 | Calibrator f.a.s. (12 × 3 mL) | Code 20401 | |
05947626160 | PreciControl ClinChem Multi 1 (4 × 5 mL) | Code 20391 | |
05947774160 | PreciControl ClinChem Multi 2 (4 × 5 mL) | Code 20392 | |
08063494190 | Diluent NaCl 9 % (123 mL) | System‑ID 2906 001 |
CHE2-T: ACN 20370
Ready for use
Reporting time | 10 min | ||
Wavelength (sub/main) | 700/415 nm | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 78 µL | – | |
R3 | 16 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 1.3 µL | – | – |
Decreased | 2.6 µL | 20 µL | 60 µL |
Increased | 1.3 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 |
Calibrators | S1: H2O |
Calibration mode | Linear |
Calibration frequency | Automatic full calibration Full calibration |
Calibration interval may be extended based on acceptable verification of calibration by the laboratory.
Traceability: This test has been standardized against a reference method using a manual application of the butyrylthiocholine/hexacyanoferrate (IlI) method on a manual photometer and the published molar absorptivity ε of hexacyanoferrate (III).
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 |
PCCC1 a) | 5606 | 24.0 | 0.4 |
PCCC2 b) | 9093 | 45.4 | 0.5 |
Human serum 1 | 245 | 14.4 | 5.9 |
Human serum 2 | 1990 | 14.8 | 0.7 |
Human serum 3 | 7260 | 49.9 | 0.7 |
Human serum 4 | 8871 | 49.4 | 0.6 |
Human serum 5 | 12278 | 60.3 | 0.5 |
Intermediate precision | Mean | SD | CV |
PCCC1 FREFPreciControl ClinChem Multi 1 | 5658 | 41.1 | 0.7 |
PCCC2 FREFPreciControl ClinChem Multi 2 | 9093 | 66.2 | 0.7 |
Human serum 1 | 245 | 14.4 | 5.9 |
Human serum 2 | 1990 | 17.7 | 0.9 |
Human serum 3 | 7260 | 56.7 | 0.8 |
Human serum 4 | 8871 | 60.9 | 0.7 |
Human serum 5 | 12272 | 76.0 | 0.6 |
Cholinesterase 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).
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 = 1.026x - 77.4 U/L | y = 1.030x - 90.4 U/L |
τ = 0.992 | r = 1.000 |
The sample activities were between 264 and 13566 U/L.
Cholinesterase values for human serum and plasma samples obtained on a cobas c 303 analyzer (y) were compared with those determined using the corresponding reagent on a cobas c 501 analyzer (x).
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 = 0.995x + 27.7 U/L | y = 0.999x + 14.5 U/L |
τ = 0.981 | r = 0.999 |
The sample concentrations were between 187 and 13388 U/L.
Cholinesterase (pseudocholinesterase or cholinesterase II) is found in the liver, pancreas, heart, serum and in the white matter of the brain. This enzyme must not be confused with acetylcholinesterase from erythrocytes (EC 3.1.1.7), which is also referred to as cholinesterase I.
The biological function of cholinesterase is unknown. Serum cholinesterase serves as an indicator of possible insecticide poisoning. It is measured as an index of liver function. In preoperative screening, cholinesterase is used to detect patients with atypical forms of the enzyme and hence avoid prolonged apnea caused by slow elimination of muscle relaxants.
Depressed cholinesterase levels are found in cases of intoxication with organophosphorus compounds and in hepatitis, cirrhosis, myocardial infarction, acute infections and atypical phenotypes of the enzyme. This assay is based on the method published by Schmidt et al.
R1 | Pyrophosphate buffer: 92 mmol/L, pH 7.7; potassium hexacyanoferrate (III): 2.4 mmol/L |
R3 | GOOD's buffer: 10 mmol/L, pH 4.0; butyrylthiocholine: 46 mmol/L; stabilizers |
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.
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
Plasma: Li‑heparin and K2‑EDTA plasma
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.
Stability: LREFTietz NW, ed. Clinical Guide to Laboratory Tests, 3rd ed. Philadelphia PA: WB Saunders Company 1995;132-133. ,LREFUse of Anticoagulants in Diagnostic Laboratory Investigations. WHO Publication WHO/DIL/LAB/99.1 Rev. 2: Jan 2002. ,LREFHuizenga JR, van der Belt K, Gips CH. The Effect of Storage at Different Temperatures on Cholinesterase Activity in Human Serum. J Clin Chem Clin Biochem 1985;24:283-385. | 6 hours at 15‑25 °C |
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.
In vitro test for the quantitative determination of cholinesterase in human serum and plasma on Roche/Hitachi cobas c systems.
butyrylthiocholine + H2O | CHE | thiocholine + butyrate |
thiocholine + potassium hexacyanoferrate (III) |
|
dithiobis(choline) + potassium hexacyanoferrate (II) |
Cholinesterase catalyzes the hydrolysis of butyrylthiocholine to thiocholine and butyrate. Thiocholine instantaneously reduces the yellow hexacyanoferrate (III) to the almost colorless hexacyanoferrate (II). This decrease in color can be measured photometrically.
To determine the dibucaine number (DN), cholinesterase activity is measured with and without enzyme inhibitor dibucaine. The dibucaine number is calculated as follows:
DN = 100 − | CHE activity with inhibitor | × 100 |
Total cholinesterase (CHE2‑T, ACN 20370)
100‑14000 U/L (1.67‑234 µkat/L)
Inhibited cholinesterase (CHE2‑D, ACN 20371)
250‑7000 U/L (4.18‑117 µkat/L)
Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:2 dilution. Results from samples diluted using the rerun function are automatically multiplied by a factor of 2.
Limit of Blank, Limit of Detection and Limit of Quantitation
Limit of Blank | = 100 U/L (1.67 µkat/L) |
Limit of Detection | = 100 U/L (1.67 µkat/L) |
Limit of Quantitation | = 100 U/L (1.67 µkat/L) |
Limit of Blank | = 250 U/L (4.18 µkat/L) |
Limit of Detection | = 250 U/L (4.18 µkat/L) |
Limit of Quantitation | = 250 U/L (4.18 µkat/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 activity 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 activity samples.
The Limit of Detection corresponds to the lowest analyte activity which can be detected (value above the Limit of Blank with a probability of 95 %).
The Limit of Quantitation is the lowest analyte activity that can be reproducibly measured with a total error of 20 %. It has been determined using low activity cholinesterase samples.
Calculated with a temperature conversion factor of 1.52 (25 → 37 °C)
Children, men, women (aged 40 years or more): 5320‑12920 U/L
Women aged 16‑39 years, not pregnant, not taking hormonal contraceptives: 4260‑11250 U/L
Women aged 18‑41 years, pregnant or taking contraceptives: 3650‑9120 U/L
Children, men, women (aged 40 years or more): 89‑215 µkat/L
Women aged 16‑39 years, not pregnant, not taking hormonal contraceptives: 71‑187 µkat/L
Women aged 18‑41 years, pregnant or taking contraceptives: 61‑152 µkat/L
*calculated by unit conversion factor
Normal individuals | UU | Dibucaine number | ≥ 73 |
Heterozygous individuals | UA | Dibucaine number | 72‑57 |
Homozygous individuals | AA | Dibucaine number | ≤ 50 |
DN results below 57 should be considered to indicate a potentially high risk of succinyldicholine sensitivity.
Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.
Total cholinesterase (CHE2‑T, ACN 20370)
Criterion: Recovery within ± 10 % of initial value at a cholinesterase activity of 5000 U/L.
Icterus:
Hemolysis:
Lipemia (Intralipid):
Drugs: No interference was found at therapeutic concentrations using common drug panels.
In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.
Inhibited cholinesterase (CHE2‑D, ACN 20371)
Criterion: Recovery within ± 10 % of initial value at a cholinesterase activity of 1250 U/L.
Icterus:
Hemolysis:
Lipemia (Intralipid):
Drugs: No interference was found at therapeutic concentrations using common drug panels.
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 Roche/Hitachi 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 | |
08105561 190 | Cholinesterase Gen.2 (1050 tests) | System‑ID 2037 001 | Roche/Hitachi cobas c 503 |
08105570 190 | Dibucaine (1050 tests) | System‑ID 2038 001 |
Materials required (but not provided):
10759350 190 | Calibrator f.a.s. (12 × 3 mL) | Code 20401 | |
10759350 360 | Calibrator f.a.s. (12 × 3 mL, for USA) | Code 20401 | |
05117003 190 | PreciControl ClinChem Multi 1 (20 × 5 mL) | Code 20391 | |
05947626 190 | PreciControl ClinChem Multi 1 (4 × 5 mL) | Code 20391 | |
05947626 160 | PreciControl ClinChem Multi 1 (4 × 5 mL, for USA) | Code 20391 | |
05117216 190 | PreciControl ClinChem Multi 2 (20 × 5 mL) | Code 20392 | |
05947774 190 | PreciControl ClinChem Multi 2 (4 × 5 mL) | Code 20392 | |
05947774 160 | PreciControl ClinChem Multi 2 (4 × 5 mL, for USA) | Code 20392 | |
08063494 190 | Diluent NaCl 9 % (123 mL) | System‑ID 2906 001 |
CHE2-T: ACN 20370, total cholinesterase
CHE2-D: ACN 20371, inhibited cholinesterase
Ready for use
Reporting time | 10 min | ||
Wavelength (sub/main) | 700/415 nm | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 78 µL | – | |
R3 | 16 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 1.3 µL | – | – |
Decreased | 2.6 µL | 20 µL | 60 µL |
Increased | 1.3 µL | – | – |
Reporting time | 10 min | ||
Wavelength (sub/main) | 700/415 nm | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 75 µL | – | |
R2 (Special Reagent) | 15 µL | – | |
R3 | 18 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 1.5 µL | – | – |
Decreased | 1.5 µL | – | – |
Increased | 1.5 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 |
Calibrators | S1: H2O |
Calibration mode | Linear |
Calibration frequency | Automatic full calibration Full calibration |
Calibration interval may be extended based on acceptable verification of calibration by the laboratory.
Traceability: This test has been standardized against a reference method using a manual application of the butyrylthiocholine/hexacyanoferrate (IlI) method on a manual photometer and the published molar absorptivity ε of hexacyanoferrate (III).
Application for inhibited cholinesterase (CHE2-D, ACN 20371)
Transfer of calibration from application for total cholinesterase (CHE2-T, ACN 20370).
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). The following results were obtained:
Repeatability | Mean | SD | CV |
PCCC1a) | 5606 | 24.0 | 0.4 |
PCCC2b) | 9093 | 45.4 | 0.5 |
Human serum 1 | 245 | 14.4 | 5.9 |
Human serum 2 | 1990 | 14.8 | 0.7 |
Human serum 3 | 7260 | 49.9 | 0.7 |
Human serum 4 | 8871 | 49.4 | 0.6 |
Human serum 5 | 12278 | 60.3 | 0.5 |
Intermediate precision | Mean | SD | CV |
PCCC1a) | 5658 | 41.1 | 0.7 |
PCCC2b) | 9093 | 66.2 | 0.7 |
Human serum 1 | 245 | 14.4 | 5.9 |
Human serum 2 | 1990 | 17.7 | 0.9 |
Human serum 3 | 7260 | 56.7 | 0.8 |
Human serum 4 | 8871 | 60.9 | 0.7 |
Human serum 5 | 12272 | 76.0 | 0.6 |
Repeatability | Mean | SD | CV |
PCCC1a) | 1463 | 22.6 | 1.5 |
PCCC2b) | 2412 | 20.3 | 0.8 |
Human serum 1 | 482 | 25.4 | 5.3 |
Human serum 2 | 1889 | 23.3 | 1.2 |
Human serum 3 | 2293 | 25.2 | 1.1 |
Human serum 4 | 3189 | 40.3 | 1.3 |
Human serum 5 | 6034 | 45.1 | 0.7 |
Intermediate precision | Mean | SD | CV |
PCCC1 FREFPreciControl ClinChem Multi 1 | 1463 | 25.2 | 1.7 |
PCCC2 FREFPreciControl ClinChem Multi 2 | 2363 | 29.7 | 1.3 |
Human serum 1 | 482 | 28.3 | 5.9 |
Human serum 2 | 1848 | 30.9 | 1.7 |
Human serum 3 | 2315 | 40.1 | 1.7 |
Human serum 4 | 3129 | 43.4 | 1.4 |
Human serum 5 | 6034 | 57.3 | 0.9 |
Total cholinesterase values for human serum and plasma samples obtained on a Roche/Hitachi cobas c 503 analyzer (y) were compared with those determined using the corresponding reagent on a Roche/Hitachi cobas c 501 analyzer (x).
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 = 1.026x - 77.4 U/L | y = 1.030x - 90.4 U/L |
τ = 0.992 | r = 1.000 |
The sample activities were between 264 and 13566 U/L.
Cholinesterase values for human serum and plasma samples obtained on a Roche/Hitachi cobas c 503 analyzer using the application for inhibited cholinesterase CHE2‑D (y) were compared with those determined using the application for total cholinesterase CHE2‑T on the same analyzer (x).
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 = 0.259x + 37.4 U/L | y = 0.259x + 51.6 U/L |
τ = 0.975 | r = 0.998 |
The sample activities were between 279 and 13941 U/L.
Cholinesterase (pseudocholinesterase or cholinesterase II) is found in the liver, pancreas, heart, serum and in the white matter of the brain. This enzyme must not be confused with acetylcholinesterase from erythrocytes (EC 3.1.1.7), which is also referred to as cholinesterase I.
The biological function of cholinesterase is unknown. Serum cholinesterase serves as an indicator of possible insecticide poisoning. It is measured as an index of liver function. In preoperative screening, cholinesterase is used to detect patients with atypical forms of the enzyme and hence avoid prolonged apnea caused by slow elimination of muscle relaxants.
At least 6 different genetic variants of serum cholinesterase have been described (A, F, J, K, S and U). The normal most common phenotype is designated U. The atypical forms A, F and S are described by high resistance to dibucaine inhibition (A), increased resistance to fluoride inhibition (F), and absence of catalytic activity (S). The homozygous forms AA or FF are found in only 0.3 to 0.5 % of the Caucasian population. The genotypes most susceptible to prolonged anesthesia and/or apnea after succinyldicholine administration are AA, AS, and SS (severe risk); AF, FS, and FF (moderate risk); and to some extent, UA (usually only during pregnancy). In such cases succinyldicholine anesthesia should be avoided. Measurements of total serum cholinesterase activity as well as determination of dibucaine number and fluoride number are needed to characterize cholinesterase variants fully. The dibucaine number indicates the percentage inhibition of enzyme activity in the presence of a standard concentration of dibucaine.
Depressed cholinesterase levels are found in cases of intoxication with organophosphorus compounds and in hepatitis, cirrhosis, myocardial infarction, acute infections and atypical phenotypes of the enzyme. This assay is based on the method published by Schmidt et al.
R1 | Pyrophosphate buffer: 92 mmol/L, pH 7.7; potassium hexacyanoferrate (III): 2.4 mmol/L |
R3 | GOOD's buffer: 10 mmol/L, pH 4.0; butyrylthiocholine: 46 mmol/L; stabilizers |
R1 is in position B and R3 is in position C.
R2 | Dibucaine: 2.6 mmol/L, pH 6.3 |
R2 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.
Total cholinesterase (CHE2-T, ACN 20370)
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
Plasma: Li‑heparin and K2‑EDTA plasma
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.
Stability: LREFTietz NW, ed. Clinical Guide to Laboratory Tests, 3rd ed. Philadelphia PA: WB Saunders Company 1995;132-133. ,LREFUse of Anticoagulants in Diagnostic Laboratory Investigations. WHO Publication WHO/DIL/LAB/99.1 Rev. 2: Jan 2002. ,LREFHuizenga JR, van der Belt K, Gips CH. The Effect of Storage at Different Temperatures on Cholinesterase Activity in Human Serum. J Clin Chem Clin Biochem 1985;24:283-385. | 6 hours at 15‑25 °C |
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.
In vitro test for the quantitative determination of cholinesterase in human serum and plasma on Roche/Hitachi cobas c systems.
butyrylthiocholine + H2O | CHE | thiocholine + butyrate |
thiocholine + potassium hexacyanoferrate (III) | |
dithiobis(choline) + potassium hexacyanoferrate (II) |
Cholinesterase catalyzes the hydrolysis of butyrylthiocholine to thiocholine and butyrate. Thiocholine instantaneously reduces the yellow hexacyanoferrate (III) to the almost colorless hexacyanoferrate (II). This decrease in color can be measured photometrically.
To determine the dibucaine number (DN), cholinesterase activity is measured with and without enzyme inhibitor dibucaine. The dibucaine number is calculated as follows:
DN = 100 − | CHE activity with inhibitor | × 100 |
Total cholinesterase (CHE2‑T, ACN 20370)
100‑14000 U/L (1.67‑234 µkat/L)
Inhibited cholinesterase (CHE2‑D, ACN 20371)
250‑7000 U/L (4.18‑117 µkat/L)
Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:2 dilution. Results from samples diluted using the rerun function are automatically multiplied by a factor of 2.
Limit of Blank, Limit of Detection and Limit of Quantitation
Limit of Blank | = 100 U/L (1.67 µkat/L) |
Limit of Detection | = 100 U/L (1.67 µkat/L) |
Limit of Quantitation | = 100 U/L (1.67 µkat/L) |
Limit of Blank | = 250 U/L (4.18 µkat/L) |
Limit of Detection | = 250 U/L (4.18 µkat/L) |
Limit of Quantitation | = 250 U/L (4.18 µkat/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 activity 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 activity samples.
The Limit of Detection corresponds to the lowest analyte activity which can be detected (value above the Limit of Blank with a probability of 95 %).
The Limit of Quantitation is the lowest analyte activity that can be reproducibly measured with a total error of 20 %. It has been determined using low activity cholinesterase samples.
Calculated with a temperature conversion factor of 1.52 (25 → 37 °C)
Children, men, women (aged 40 years or more): 5320‑12920 U/L
Women aged 16‑39 years, not pregnant, not taking hormonal contraceptives: 4260‑11250 U/L
Women aged 18‑41 years, pregnant or taking contraceptives: 3650‑9120 U/L
Children, men, women (aged 40 years or more): 89‑215 µkat/L
Women aged 16‑39 years, not pregnant, not taking hormonal contraceptives: 71‑187 µkat/L
Women aged 18‑41 years, pregnant or taking contraceptives: 61‑152 µkat/L
*calculated by unit conversion factor
Normal individuals | UU | Dibucaine number | ≥ 73 |
Heterozygous individuals | UA | Dibucaine number | 72‑57 |
Homozygous individuals | AA | Dibucaine number | ≤ 50 |
DN results below 57 should be considered to indicate a potentially high risk of succinyldicholine sensitivity.
Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.
Total cholinesterase (CHE2‑T, ACN 20370)
Criterion: Recovery within ± 10 % of initial value at a cholinesterase activity of 5000 U/L.
Icterus:
Hemolysis:
Lipemia (Intralipid):
Drugs: No interference was found at therapeutic concentrations using common drug panels.
In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.
Inhibited cholinesterase (CHE2‑D, ACN 20371)
Criterion: Recovery within ± 10 % of initial value at a cholinesterase activity of 1250 U/L.
Icterus:
Hemolysis:
Lipemia (Intralipid):
Drugs: No interference was found at therapeutic concentrations using common drug panels.
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 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 | |||
08105561190 | Cholinesterase Gen.2 (1050 tests) | System‑ID 2037 001 |
Materials required (but not provided):
08105570190 | Dibucaine (1050 tests) | System‑ID 2038 001 | |
10759350190 | Calibrator f.a.s. (12 × 3 mL) | Code 20401 | |
05117003190 | PreciControl ClinChem Multi 1 (20 × 5 mL) | Code 20391 | |
05947626190 | PreciControl ClinChem Multi 1 (4 × 5 mL) | Code 20391 | |
05117216190 | PreciControl ClinChem Multi 2 (20 × 5 mL) | Code 20392 | |
05947774190 | PreciControl ClinChem Multi 2 (4 × 5 mL) | Code 20392 | |
08063494190 | Diluent NaCl 9 % (123 mL) | System‑ID 2906 001 |
CHE2-T: ACN 20370, total cholinesterase
CHE2-D: ACN 20371, inhibited cholinesterase
Ready for use
Reporting time | 10 min | ||
Wavelength (sub/main) | 700/415 nm | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 78 µL | – | |
R3 | 16 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 1.3 µL | – | – |
Decreased | 2.6 µL | 20 µL | 60 µL |
Increased | 1.3 µL | – | – |
Reporting time | 10 min | ||
Wavelength (sub/main) | 700/415 nm | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 75 µL | – | |
R2 (Special Reagent) | 15 µL | – | |
R3 | 18 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 1.5 µL | – | – |
Decreased | 1.5 µL | – | – |
Increased | 1.5 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 |
Calibrators | S1: H2O |
Calibration mode | Linear |
Calibration frequency | Automatic full calibration Full calibration |
Calibration interval may be extended based on acceptable verification of calibration by the laboratory.
Traceability: This test has been standardized against a reference method using a manual application of the butyrylthiocholine/hexacyanoferrate (IlI) method on a manual photometer and the published molar absorptivity ε of hexacyanoferrate (III).
Application for inhibited cholinesterase (CHE2-D, ACN 20371)
Transfer of calibration from application for total cholinesterase (CHE2-T, ACN 20370).
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 |
PCCC1a) | 5606 | 24.0 | 0.4 |
PCCC2b) | 9093 | 45.4 | 0.5 |
Human serum 1 | 245 | 14.4 | 5.9 |
Human serum 2 | 1990 | 14.8 | 0.7 |
Human serum 3 | 7260 | 49.9 | 0.7 |
Human serum 4 | 8871 | 49.4 | 0.6 |
Human serum 5 | 12278 | 60.3 | 0.5 |
Intermediate precision | Mean | SD | CV |
PCCC1a) | 5658 | 41.1 | 0.7 |
PCCC2b) | 9093 | 66.2 | 0.7 |
Human serum 1 | 245 | 14.4 | 5.9 |
Human serum 2 | 1990 | 17.7 | 0.9 |
Human serum 3 | 7260 | 56.7 | 0.8 |
Human serum 4 | 8871 | 60.9 | 0.7 |
Human serum 5 | 12272 | 76.0 | 0.6 |
Repeatability | Mean | SD | CV |
PCCC1a) | 1463 | 22.6 | 1.5 |
PCCC2b) | 2412 | 20.3 | 0.8 |
Human serum 1 | 482 | 25.4 | 5.3 |
Human serum 2 | 1889 | 23.3 | 1.2 |
Human serum 3 | 2293 | 25.2 | 1.1 |
Human serum 4 | 3189 | 40.3 | 1.3 |
Human serum 5 | 6034 | 45.1 | 0.7 |
Intermediate precision | Mean | SD | CV |
PCCC1 FREFPreciControl ClinChem Multi 1 | 1463 | 25.2 | 1.7 |
PCCC2 FREFPreciControl ClinChem Multi 2 | 2363 | 29.7 | 1.3 |
Human serum 1 | 482 | 28.3 | 5.9 |
Human serum 2 | 1848 | 30.9 | 1.7 |
Human serum 3 | 2315 | 40.1 | 1.7 |
Human serum 4 | 3129 | 43.4 | 1.4 |
Human serum 5 | 6034 | 57.3 | 0.9 |
Total cholinesterase values for human serum and plasma samples obtained on
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 = 1.026x - 77.4 U/L | y = 1.030x - 90.4 U/L |
τ = 0.992 | r = 1.000 |
The sample activities were between 264 and 13566 U/L.
Cholinesterase values for human serum and plasma samples obtained on
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 = 0.259x + 37.4 U/L | y = 0.259x + 51.6 U/L |
τ = 0.975 | r = 0.998 |
The sample activities were between 279 and 13941 U/L.
Total cholinesterase values for human serum and plasma samples obtained on a cobas c 303 analyzer (y) were compared with those determined using the corresponding reagent on a cobas c 501 analyzer (x).
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 = 0.995x + 27.7 U/L | y = 0.999x + 14.5 U/L |
τ = 0.981 | r = 0.999 |
The sample activities were between 187 and 13388 U/L.
Cholinesterase values for human serum and plasma samples obtained on a cobas c 303 analyzer using the application for inhibited cholinesterase CHE2‑D (y) were compared with those determined using the application for total cholinesterase CHE2‑T on the same analyzer (x).
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 = 0.258x - 8.95 U/L | y = 0.255x + 24.1 U/L |
τ = 0.937 | r = 0.996 |
The sample activities were between 1219 and 13696 U/L.
Cholinesterase (pseudocholinesterase or cholinesterase II) is found in the liver, pancreas, heart, serum and in the white matter of the brain. This enzyme must not be confused with acetylcholinesterase from erythrocytes (EC 3.1.1.7), which is also referred to as cholinesterase I.
The biological function of cholinesterase is unknown. Serum cholinesterase serves as an indicator of possible insecticide poisoning. It is measured as an index of liver function. In preoperative screening, cholinesterase is used to detect patients with atypical forms of the enzyme and hence avoid prolonged apnea caused by slow elimination of muscle relaxants.
At least 6 different genetic variants of serum cholinesterase have been described (A, F, J, K, S and U). The normal most common phenotype is designated U. The atypical forms A, F and S are described by high resistance to dibucaine inhibition (A), increased resistance to fluoride inhibition (F), and absence of catalytic activity (S). The homozygous forms AA or FF are found in only 0.3 to 0.5 % of the Caucasian population. The genotypes most susceptible to prolonged anesthesia and/or apnea after succinyldicholine administration are AA, AS, and SS (severe risk); AF, FS, and FF (moderate risk); and to some extent, UA (usually only during pregnancy). In such cases succinyldicholine anesthesia should be avoided. Measurements of total serum cholinesterase activity as well as determination of dibucaine number and fluoride number are needed to characterize cholinesterase variants fully. The dibucaine number indicates the percentage inhibition of enzyme activity in the presence of a standard concentration of dibucaine.
Depressed cholinesterase levels are found in cases of intoxication with organophosphorus compounds and in hepatitis, cirrhosis, myocardial infarction, acute infections and atypical phenotypes of the enzyme. This assay is based on the method published by Schmidt et al.
R1 | Pyrophosphate buffer: 92 mmol/L, pH 7.7; potassium hexacyanoferrate (III): 2.4 mmol/L |
R3 | GOOD's buffer: 10 mmol/L, pH 4.0; butyrylthiocholine: 46 mmol/L; stabilizers |
R1 is in position B and R3 is in position C.
R2 | Dibucaine: 2.6 mmol/L, pH 6.3 |
R2 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.
Total cholinesterase (CHE2-T, ACN 20370)
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
Plasma: Li‑heparin and K2‑EDTA plasma
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.
Stability: LREFTietz NW, ed. Clinical Guide to Laboratory Tests, 3rd ed. Philadelphia PA: WB Saunders Company 1995;132-133. ,LREFUse of Anticoagulants in Diagnostic Laboratory Investigations. WHO Publication WHO/DIL/LAB/99.1 Rev. 2: Jan 2002. ,LREFHuizenga JR, van der Belt K, Gips CH. The Effect of Storage at Different Temperatures on Cholinesterase Activity in Human Serum. J Clin Chem Clin Biochem 1985;24:283-385. | 6 hours at 15‑25 °C |
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.
In vitro test for the quantitative determination of the catalytic activity of cholinesterase (EC 3.1.1.8; acylcholine acylhydrolase) in serum and plasma
Method with butyrylthiocholine.
Cholinesterase catalyzes the hydrolysis of butyrylthiocholine to thiocholine and butyrate. Thiocholine instantaneously reduces the yellow hexacyanoferrate (III) to the almost colorless hexacyanoferrate (II). This decrease in color can be measured at wavelengths between 405 and 415 nm.
butyrylthiocholine + H2O | CHE | thiocholine + butyrate |
thiocholine + potassium hexacyanoferrate (III) | |
dithiobis(choline) + potassium hexacyanoferrate (II) |
200‑14000 U/L (3.34‑234 µkat/L)
Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:2 dilution. Results from samples diluted using the rerun function are automatically multiplied by a factor of 2.
Lower detection limit of the test:
200 U/L (3.34 µkat/L)
The lower detection limit represents the lowest measurable analyte level that can be distinguished from zero. It is calculated as the value lying 3 standard deviations above that of a zero sample (zero sample + 3 SD, repeatability, n = 21).
Women aged 40 years or more, children, men:
5320‑12920 U/L (89‑215 µkat/L)
Women aged 16‑39 years, not pregnant, not using hormonal contraceptives:
4260‑11250 U/L (71‑187 µkat/L)
Women aged 18‑41 years, pregnant or taking contraceptives:
3650‑9120 U/L (61‑152 µkat/L)
Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.
*Calculated with a temperature conversion factor of 1.52 (25 → 37 °C).
Criterion: Recovery within ± 10 % of initial value.
Icterus:
Hemolysis:
Lipemia (Intralipid):
Drugs: No interference was found at therapeutic concentrations using common drug panels.
Anticoagulants: Citrate and fluoride inhibit the reaction and must not be used.
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 COBAS INTEGRA analyzers. Refer to the CLEAN Method Sheet for further instructions and for the latest version of the Extra wash cycle list.
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 | |||
04498577 190 | Cholinesterase Gen.2 (200 tests) | System-ID 07 6842 1 | COBAS INTEGRA 400 plus |
Materials required (but not provided):
10759350 190 | Calibrator f.a.s. (12 × 3 mL) | System-ID 07 3718 6 | |
10759350 360 | Calibrator f.a.s. (12 × 3 mL, for USA) | System-ID 07 3718 6 | |
12149435 122 | Precinorm U plus (10 × 3 mL) | System-ID 07 7999 7 | |
12149435 160 | Precinorm U plus (10 × 3 mL, for USA) | System-ID 07 7999 7 | |
12149443 122 | Precipath U plus (10 × 3 mL) | System-ID 07 8000 6 | |
12149443 160 | Precipath U plus (10 × 3 mL, for USA) | System-ID 07 8000 6 | |
05117003 190 | PreciControl ClinChem Multi 1 (20 × 5 mL) | System-ID 07 7469 3 | |
05947626 190 | PreciControl ClinChem Multi 1 (4 × 5 mL) | System-ID 07 7469 3 | |
05947626 160 | PreciControl ClinChem Multi 1 (4 × 5 mL, for USA) | System-ID 07 7469 3 | |
05117216 190 | PreciControl ClinChem Multi 2 (20 × 5 mL) | System-ID 07 7470 7 | |
05947774 190 | PreciControl ClinChem Multi 2 (4 × 5 mL) | System-ID 07 7470 7 | |
05947774 160 | PreciControl ClinChem Multi 2 (4 × 5 mL, for USA) | System-ID 07 7470 7 |
Test CHE2, test ID 0‑021
Ready for use
Measuring mode | Absorbance |
Abs. calculation mode | Kinetic |
Reaction mode | R1‑S‑SR |
Reaction direction | Decrease |
Wavelength A/B | 409/659 nm |
Calc. first/last | 43/52 |
Unit | U/L |
Diluent (H2O) | ||
R1 | 120 µL | |
Sample | 2 µL | 5 µL |
SR | 24 µL | |
151 µL |
Shelf | See expiration date on cobas c pack label |
On-board in use at 10‑15 °C | 4 |
Calibrator | Calibrator f.a.s. Use deionized water as zero calibrator. |
Calibration mode | Linear regression |
Calibration replicate | Duplicate recommended |
Calibration interval | Each lot |
Calibration interval may be extended based on acceptable verification of calibration by the laboratory.
Traceability: This test is standardized against a reference method using a manual application of the butyrylthiocholine/hexacyanoferrate (III) method on a photometer and the published molar absorptivity of hexacyanoferrate (III).
Representative performance data on the COBAS INTEGRA analyzers are given below. Results obtained in individual laboratories may differ.
Precision was determined using human samples and controls in an internal protocol with repeatability (n = 21) and intermediate precision (1 aliquot per run, 1 run per day, 21 days). The following results were obtained:
Repeatability | Intermediate precision | |||||
|---|---|---|---|---|---|---|
Sample | Mean | CV | Mean | CV | ||
U/L | µkat/L | % | U/L | µkat/L | % | |
Human serum | 6374 | 106 | 0.5 | 6675 | 111 | 1.4 |
Precinorm U | 6263 | 105 | 0.6 | 6213 | 104 | 1.1 |
Precipath U | 6015 | 100 | 0.6 | 5964 | 100 | 0.9 |
CHE values for human serum samples obtained on a COBAS INTEGRA 800 analyzer using the Roche CHE2 reagent (y) were compared with those determined using the Roche CHE reagent on the same analyzer (x).
Sample size (n) = 51
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 = 0.970× + 128 (U/L) т = 0.967 SD (md95) = 125 | y = 0.965× + 153 (U/L) r = 0.999 Sy.x = 37.1 |
The sample activities were between 1192 U/L and 14411 U/L (19.9‑241 µkat/L).
Cholinesterase (pseudocholinesterase or cholinesterase II) is found in the liver, pancreas, heart, serum and in the white matter of the brain. This enzyme must not be confused with acetylcholinesterase from erythrocytes (EC 3.1.1.7), which is also referred to as cholinesterase I.
The biological function of cholinesterase is unknown. Serum cholinesterase serves as an indicator of possible insecticide poisoning. It is measured as an index of liver function. In pre‑operative screening, cholinesterase is used to detect patients with atypical forms of the enzyme and hence avoid prolonged apnea caused by slow elimination of muscle relaxants.
Depressed cholinesterase levels are found in cases of intoxication with organophosphorus compounds and in hepatitis, cirrhosis, myocardial infarction, acute infections and atypical phenotypes of the enzyme.
This assay is based on the method published by Schmidt E et al. in 1992.
R1 | Pyrophosphate buffer: 92 mmol/L, pH 7.7; potassium hexacyanoferrate : 2.4 mmol/L |
SR | GOOD's buffer: 10 mmol/L, pH 4.0; butyrylthiocholine: 46 mmol/L; stabilizers |
R1 is in position B and SR 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.
Reference range | |
Pathological range | |
Control interval | 24 hours recommended |
Control sequence | User defined |
Control after calibration | Recommended |
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: Li‑heparin, K2‑EDTA or K3‑EDTA plasma.
Do not use citrate and fluoride plasma.
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.
Stability: LREFTietz NW, ed. Clinical Guide to Laboratory Tests, 3rd ed. Philadelphia PA: WB Saunders Company 1995;132-133. ,LREFUse of Anticoagulants in Diagnostic Laboratory Investigations. WHO Publication WHO/DIL/LAB/99.1 Rev. 2: Jan 2002. ,LREFHuizenga JR, van der Belt K, Gips CH. The Effect of Storage at Different Temperatures on Cholinesterase Activity in Human Serum. J Clin Chem Clin Biochem 1985;24:283-385. | 6 hours at 15‑25 °C 7 days at 2‑8 °C 1 year at ‑20 °C |
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.
In vitro test for the quantitative determination of cholinesterase in human serum and plasma on Roche/Hitachi cobas c systems.
Colorimetric assay
CHE | ||
butyrylthiocholine + H2O |
| thiocholine + butyrate |
thiocholine + potassium hexacyanoferrate (III) |
dithiobis(choline) + potassium hexacyanoferrate (II) |
Cholinesterase catalyzes the hydrolysis of butyrylthiocholine to thiocholine and butyrate. Thiocholine instantaneously reduces the yellow hexacyanoferrate (III) to the almost colorless hexacyanoferrate (II). This decrease in color can be measured photometrically.
Measuring range
100‑14000 U/L (1.67‑234 µkat/L)
Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:2 dilution. Results from samples diluted using the rerun function are automatically multiplied by a factor of 2.
Lower limits of measurement
Lower detection limit of the test
100 U/L (1.67 µkat/L)
The lower detection limit represents the lowest measurable analyte level that can be distinguished from zero. It is calculated as the value lying 3 standard deviations above that of the lowest standard (standard 1 + 3 SD, repeatability, n = 21).
Children, men, women (aged 40 years or more): 5320‑12920 U/L (89‑215.3 µkat/L)
Women aged 16‑39 years, not pregnant, not taking hormonal contraceptives: 4260‑11250 U/L (71‑187 µkat/L)
Women aged 18‑41 years, pregnant or taking contraceptives: 3650‑9120 U/L (61‑152 µkat/L)
Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.
Roche has not evaluated reference ranges in a pediatric population.
a) Calculated with a temperature conversion factor of 1.52 (25 → 37 °C)
Criterion: Recovery within ± 10 % of initial values at a cholinesterase activity of 5000 U/L (83.5 µkat/L).
Icterus:
Hemolysis:
Lipemia (Intralipid):
Drugs: No interference was found at therapeutic concentrations using common drug panels.
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 Roche/Hitachi 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,
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 | |
04498577 190 | Cholinesterase Gen.2 (200 tests) | System‑ID 07 6842 1 | Roche/Hitachi cobas c 311, cobas c 501/502 |
Materials required (but not provided):
10759350 190 | Calibrator f.a.s. (12 x 3 mL) | Code 401 | |
10759350 360 | Calibrator f.a.s. (12 x 3 mL, for USA) | Code 401 | |
12149435 122 | Precinorm U plus (10 x 3 mL) | Code 300 | |
12149435 160 | Precinorm U plus (10 x 3 mL, for USA) | Code 300 | |
12149443 122 | Precipath U plus (10 x 3 mL) | Code 301 | |
12149443 160 | Precipath U plus (10 x 3 mL, for USA) | Code 301 | |
10171743 122 | Precinorm U (20 x 5 mL) | Code 300 | |
10171735 122 | Precinorm U (4 x 5 mL) | Code 300 | |
10171778 122 | Precipath U (20 x 5 mL) | Code 301 | |
10171760 122 | Precipath U (4 x 5 mL) | Code 301 | |
05117003 190 | PreciControl ClinChem Multi 1 (20 x 5 mL) | Code 391 | |
05947626 190 | PreciControl ClinChem Multi 1 (4 x 5 mL) | Code 391 | |
05947626 160 | PreciControl ClinChem Multi 1 (4 x 5 mL, for USA) | Code 391 | |
05117216 190 | PreciControl ClinChem Multi 2 (20 x 5 mL) | Code 392 | |
05947774 190 | PreciControl ClinChem Multi 2 (4 x 5 mL) | Code 392 | |
05947774 160 | PreciControl ClinChem Multi 2 (4 x 5 mL, for USA) | Code 392 | |
04489357 190 | Diluent NaCl 9 % (50 mL) | System‑ID 07 6869 3 |
For cobas c 311/501 analyzers:
CHE2: ACN 510
For cobas c 502 analyzer:
CHE2: ACN 8510
Ready for use
cobas c 311 test definition | |||
Assay type | Rate A | ||
Reaction time / Assay points | 10 / 29‑40 | ||
Wavelength (sub/main) | 700/415 nm | ||
Reaction direction | Decrease | ||
Units | U/L (µkat/L, kU/L) | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 120 µL | – | |
R3 | 24 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 2 µL | – | – |
Decreased | 10 µL | 15 µL | 135 µL |
Increased | 2 µL | – | – |
cobas c 501 test definition | |||
Assay type | Rate A | ||
Reaction time / Assay points | 10 / 44‑54 | ||
Wavelength (sub/main) | 700/415 nm | ||
Reaction direction | Decrease | ||
Units | U/L (µkat/L, kU/L) | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 120 µL | – | |
R3 | 24 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 2 µL | – | – |
Decreased | 10 µL | 15 µL | 135 µL |
Increased | 2 µL | – | – |
cobas c 502 test definition | |||
Assay type | Rate A | ||
Reaction time / Assay points | 10 / 44‑54 | ||
Wavelength (sub/main) | 700/415 nm | ||
Reaction direction | Decrease | ||
Units | U/L (µkat/L, kU/L) | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 120 µL | – | |
R3 | 24 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 2 µL | – | – |
Decreased | 10 µL | 15 µL | 135 µL |
Increased | 4 µL | – | – |
CHE2 | |
Shelf life at 2‑8 °C: | See expiration date on cobas c pack label. |
On‑board in use and refrigerated on the analyzer: | 4 weeks |
Diluent NaCl 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 |
Calibrators | S1: H2O S2: C.f.a.s. |
Calibration mode | Linear |
Calibration frequency | 2‑point calibration |
Calibration interval may be extended based on acceptable verification of calibration by the laboratory.
Traceability: This test has been standardized against a reference method using a manual application of the butyrylthiocholine/hexacyanoferrate (IlI) method on a manual photometer and the published molar absorptivity ε of hexacyanoferrate (III).
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 an internal protocol with repeatability (n = 21) and intermediate precision (3 aliquots per run, 1 run per day, 21 days). The following results were obtained:
Repeatability | Mean U/L (µkat/L) | SD U/L (µkat/L) | CV % |
Precinorm U | 4887 (81.6) | 25 (0.4) | 0.5 |
Precipath U | 5331 (89.0) | 27 (0.5) | 0.5 |
Human serum 1 | 5916 (98.8) | 28 (0.5) | 0.5 |
Human serum 2 | 7313 (122) | 38 (1) | 0.5 |
Intermediate precision | Mean U/L (µkat/L) | SD U/L (µkat/L) | CV % |
Precinorm U | 4707 (78.6) | 49 (0.8) | 1.0 |
Precipath U | 4838 (80.8) | 45 (0.8) | 0.9 |
Human serum 3 | 1002 (16.7) | 26 (0.4) | 2.6 |
Human serum 4 | 6683 (112) | 74 (1) | 1.1 |
Cholinesterase values for human serum and plasma samples obtained on a Roche/Hitachi cobas c 501 analyzer (y) were compared with those determined using the corresponding reagent on a COBAS INTEGRA 700 analyzer (x).
Sample size (n) = 89
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 = 1.019x - 177 U/L | y = 1.018x - 178 U/L |
τ = 0.963 | r = 0.999 |
The sample activities were between 2184 and 12525 U/L (36.5 and 209 µkat/L). |
Cholinesterase (pseudocholinesterase or cholinesterase II) is found in the liver, pancreas, heart, serum and in the white matter of the brain. This enzyme must not be confused with acetylcholinesterase from erythrocytes (EC 3.1.1.7), which is also referred to as cholinesterase I.
The biological function of cholinesterase is unknown. Serum cholinesterase serves as an indicator of possible insecticide poisoning. It is measured as an index of liver function. In preoperative screening, cholinesterase is used to detect patients with atypical forms of the enzyme and hence avoid prolonged apnea caused by slow elimination of muscle relaxants.
Depressed cholinesterase levels are found in cases of intoxication with organophosphorus compounds and in hepatitis, cirrhosis, myocardial infarction, acute infections and atypical phenotypes of the enzyme. This assay is based on the method published by Schmidt et al.
R1 | Pyrophosphate buffer: 92 mmol/L, pH 7.7; potassium hexacyanoferrate (III): 2.4 mmol/L |
R3 | GOOD's buffer: 10 mmol/L, pH 4.0; butyrylthiocholine: 46 mmol/L; stabilizers |
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.
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.
Plasma: Li‑heparin and K2‑EDTA plasma
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.
Stability: LREFTietz NW, ed. Clinical Guide to Laboratory Tests, 3rd ed. Philadelphia PA: WB Saunders Company 1995;132-133. ,LREFUse of Anticoagulants in Diagnostic Laboratory Investigations. WHO Publication WHO/DIL/LAB/99.1 Rev. 2: Jan 2002. ,LREFHuizenga JR, van der Belt K, Gips CH. The Effect of Storage at Different Temperatures on Cholinesterase Activity in Human Serum. J Clin Chem Clin Biochem 1985;24:283-385. | 6 hours at 15‑25 °C |
7 days at 2‑8 °C | |
1 year at -20 °C |
Cholinesterase Gen.2
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