In vitro test for the quantitative determination of creatine kinase (CK) in human serum and plasma on
UV‑test
Creatine phosphate + ADP | CK | creatine + ATP |
ATP + D‑glucose | HK | ADP + G6P |
G6P + NADP+ | G6PDH | D‑6‑phosphogluconate + NADPH + H+ |
Equimolar quantities of NADPH and ATP are formed at the same rate. The photometrically measured rate of formation of NADPH is directly proportional to the CK activity.
Measuring range
7‑2000 U/L (0.12‑33.4 µkat/L)
Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:11 dilution. Results from samples diluted by the rerun function are automatically multiplied by a factor of 11.
Lower limits of measurement
Limit of Blank, Limit of Detection and Limit of Quantitation | |
Limit of Blank | = 7 U/L (0.12 µkat/L) |
Limit of Detection | = 7 U/L (0.12 µkat/L) |
Limit of Quantitation | = 7 U/L (0.12 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 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 precision of 20 % CV. It has been determined using low concentration creatine kinase samples.
Reference intervals strongly depend on the patient group and the specific clinical situation.
For healthy people, according to Klein et al.: LREFKlein G, Berger A, Bertholf R, et al. Abstract: Multicenter Evaluation of Liquid Reagents for CK, CK-MB and LDH with Determination of Reference Intervals on Hitachi Systems. Clin Chem 2001;47:Suppl. A30. | ||
CK | U/L | µkat/L |
Men | 39‑308 | 0.65‑5.14 |
Women | 26‑192 | 0.43‑3.21 |
Consensus values: LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308. | ||
CK | U/L | µkat/L |
Men | < 190 | < 3.20 |
Women | < 170 | < 2.85 |
Consensus values: LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308. | ||
CK‑MB | U/L | µkat/L |
Men/women | < 25 | < 0.42 |
Myocardial infarction: There is a high probability of myocardial damage when the following three conditions are fulfilled: LREFStein W. Strategie der klinischen-chemischen Diagnostik des frischen Myokardinfarktes. Med Welt 1985;36:572-577. | |||
U/L | µkat/L | ||
1 | CKmen | > 190 | > 3.17 |
CKwomen | > 167 | > 2.79 | |
2 | CK‑MB | > 24 | > 0.40 |
3 | The CK‑MB activity accounts for 6‑25 % of the total CK‑activity. |
According to Tietz: LREFWu AHB, editor. Tietz Clinical Guide to Laboratory Tests, 4th edition. St. Louis (MO): Saunders Elsevier 2006;306-307. | ||
CK | U/L | µkat/L |
Adult males > 19 years | 20‑200 | 0.33‑3.34 |
Adult females > 19 years | 20‑180 | 0.33‑3.01 |
The reference values according to Klein et al. are based on the 95th percentile of a group of healthy persons (202 men and 217 women) not involved in high‑intensity athletic activities.
In order to ensure high sensitivity in the diagnosis of heart diseases the values given by Tietz are recommended. The loss of diagnostic specificity thereby incurred can be compensated for by additionally determining CK‑MB and/or troponin T. When myocardial infarction is suspected the diagnostic strategy proposals in the consensus document of European and American cardiologists should in general be followed.
If despite the suspicion of myocardial infarction the values found remain below the stated limits, a fresh infarction may be involved. In such cases, the determinations should be repeated after 4 hours.
CK varies with physical activity level and race in healthy individuals.
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 a creatine kinase activity of 140 U/L (2.34 µkat/L).
Icterus:
Hemolysis:
Lipemia (Intralipid):
Drugs: No interference was found at therapeutic concentrations using common drug panels.
Cyanokit (Hydroxocobalamin) at therapeutic concentrations interferes with the test.
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. The latest version of the carry‑over evasion list can be found with the NaOHD-SMS-SmpCln1+2-SCCS Method Sheets. For further instructions refer to the operator’s manual. cobas c 502 analyzer: All special wash programming necessary for avoiding carry‑over is available via the cobas link, manual input is required in certain cases.
Where required, special wash/carry‑over evasion programming must be implemented prior to reporting results with this test.
|
| Analyzer(s) on which cobas c pack(s) can be used | |
07190794190 | Creatine Kinase (200 tests) | System-ID 07 7485 5 |
10759350190 | Calibrator f.a.s. (12 x 3 mL) | Code 401 | |
10759350360 | Calibrator f.a.s. (12 x 3 mL, for USA) | Code 401 | |
12149435122 | Precinorm U plus (10 x 3 mL) | Code 300 | |
12149435160 | Precinorm U plus (10 x 3 mL, for USA) | Code 300 | |
12149443122 | Precipath U plus (10 x 3 mL) | Code 301 | |
12149443160 | Precipath U plus (10 x 3 mL, for USA) | Code 301 | |
05117003190 | PreciControl ClinChem Multi 1 (20 x 5 mL) | Code 391 | |
05947626190 | PreciControl ClinChem Multi 1 (4 x 5 mL) | Code 391 | |
05947626160 | PreciControl ClinChem Multi 1 (4 x 5 mL, for USA) | Code 391 | |
05117216190 | PreciControl ClinChem Multi 2 (20 x 5 mL) | Code 392 | |
05947774190 | PreciControl ClinChem Multi 2 (4 x 5 mL) | Code 392 | |
05947774160 | PreciControl ClinChem Multi 2 (4 x 5 mL, for USA) | Code 392 | |
04489357190 | Diluent NaCl 9 % (50 mL) | System-ID 07 6869 3 |
For cobas c 311/501 analyzers:
CK2: ACN 550
For cobas c 502 analyzer:
CK2: ACN 8550
Ready for use
cobas c 311 test definition | |||
Assay type | Rate A | ||
Reaction time / Assay points | 10 / 16‑29 | ||
Wavelength (sub/main) | 546/340 nm | ||
Reaction direction | Increase | ||
Units | U/L (µkat/L) | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 100 µL | – | |
R2 | 20 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 2.8 µL | – | – |
Decreased | 2.8 µL | 15 µL | 150 µL |
Increased | 2.8 µL | – | – |
cobas c 501 test definition | |||
Assay type | Rate A | ||
Reaction time / Assay points | 10 / 24‑44 | ||
Wavelength (sub/main) | 546/340 nm | ||
Reaction direction | Increase | ||
Units | U/L (µkat/L) | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 100 µL | – | |
R2 | 20 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 2.8 µL | – | – |
Decreased | 2.8 µL | 15 µL | 150 µL |
Increased | 2.8 µL | – | – |
cobas c 502 test definition | |||
Assay type | Rate A | ||
Reaction time / Assay points | 10 / 24‑44 | ||
Wavelength (sub/main) | 546/340 nm | ||
Reaction direction | Increase | ||
Units | U/L (µkat/L) | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 100 µL | – | |
R2 | 20 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 2.8 µL | – | – |
Decreased | 2.8 µL | 15 µL | 150 µL |
Increased | 5.6 µL | – | – |
CK | |
Shelf life at 2‑8 °C: | See expiration date on cobas c pack label. |
On‑board in use and refrigerated on the analyzer: | 8 weeks |
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 |
Traceability: This method has been standardized against the IFCC Method for Creatine Kinase.
Representative performance data on the analyzers are given below. Results obtained in individual laboratories may differ.
Repeatability and intermediate precision were determined using human samples and controls in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP5 requirements (2 aliquots per run, 2 runs per day, 21 days). The following results were obtained:
Repeatability | Mean U/L (µkat/L) | SD U/L (µkat/L) | CV % |
|---|---|---|---|
Human serum 1 | 18.7 (0.31) | 0.6 (0.01) | 3.0 |
Human serum 2 | 137 (2.29) | 0.8 (0.01) | 0.6 |
Human serum 3 | 477 (7.97) | 3.0 (0.05) | 0.6 |
Human serum 4 | 946 (15.8) | 5.3 (0.09) | 0.6 |
Human serum 5 | 1816 (30.3) | 9.4 (0.16) | 0.5 |
PCCC Multi 1* | 154 (2.57) | 0.9 (0.02) | 0.6 |
PCCC Multi 2 | 301 (5.02) | 1.3 (0.02) | 0.4 |
Intermediate precision | Mean U/L (µkat/L) | SD U/L (µkat/L) | CV % |
|---|---|---|---|
Human serum 1 | 18.7 (0.31) | 0.6 (0.01) | 3.2 |
Human serum 2 | 137 (2.29) | 1.1 (0.02) | 0.8 |
Human serum 3 | 477 (7.97) | 3.1 (0.05) | 0.6 |
Human serum 4 | 946 (15.8) | 5.8 (0.10) | 0.6 |
Human serum 5 | 1816 (30.3) | 10 (0.17) | 0.6 |
PCCC Multi 1 | 154 (2.57) | 1.7 (0.03) | 1.1 |
PCCC Multi 2 | 301 (5.02) | 2.6 (0.04) | 0.9 |
*PCCC = PreciControl ClinChem
The data obtained on cobas c 501 analyzer(s) are representative for cobas c 311 analyzer(s).
Creatine kinase values for human serum and plasma samples obtained on a
Sample size (n) = 132
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 = 1.021x + 5.88 U/L | y = 1.006x + 13.6 U/L |
τ = 0.980 | r = 0.999 |
The sample activities were between 7.59 and 1946 U/L (0.13 and 32.5 µkat/L). |
The data obtained on cobas c 501 analyzer(s) are representative for cobas c 311 analyzer(s).
Creatine kinase (CK) is a dimeric enzyme occurring in four different forms: a mitochondrial isoenzyme and the cytosolic isoenzymes CK‑MM (skeletal muscle type), CK‑BB (brain type) and CK‑MB (myocardial type).
The determination of CK and CK‑isoenzyme activities is utilized in the diagnosis and monitoring of myocardial infarction and myopathies such as the progressive Duchenne muscular dystrophy. Following injury to the myocardium, such as occurs with acute myocardial infarction
The assay method using creatine phosphate and ADP was first described by Oliver
Standardized methods for the determination of CK with activation by NAC were recommended by the German Society for Clinical Chemistry (DGKC)
R1 | Imidazole buffer: 123 mmol/L, pH 6.5 (37 °C); EDTA: 2.46 mmol/L; Mg2+: 12.3 mmol/L; ADP: 2.46 mmol/L; AMP: 6.14 mmol/L; diadenosine pentaphosphate: 19 µmol/L; NADP+ (yeast): 2.46 mmol/L; N‑acetylcysteine: 24.6 mmol/L; HK (yeast): ≥ 36.7 µkat/L; G6PDH (E. coli): ≥ 23.4 µkat/L; preservative; stabilizers; additives. |
R2 | CAPSO* buffer: 20 mmol/L, pH 8.8 (37 °C); glucose: 120 mmol/L; EDTA: 2.46 mmol/L; creatine phosphate: 184 mmol/L; preservative; stabilizers. |
*CAPSO: 3‑(cyclohexylamine)‑2‑hydroxy‑1‑propanesulfonic acid |
R1 is in position B and 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.
This kit contains components classified as follows in accordance with the Regulation (EC) No. 1272/2008:
H360D | May damage the unborn child. |
Prevention:
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P280 | Wear protective gloves/ protective clothing/ eye protection/ face protection/ hearing protection. |
Response:
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
Storage:
P405 | Store locked up. |
Disposal:
P501 | Dispose of contents/container to an approved waste disposal plant. |
Product safety labeling follows EU GHS guidance.
Contact phone: all countries: +49-621-7590, USA: 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. 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: Nonhemolyzed serum is the specimen of choice and also recommended by IFCC.
Plasma: Li‑heparin, K2‑, K3‑EDTA plasma.
Please note: Differences in the degree of hemolysis resulting from the blood sampling procedure used can lead to deviating results in serum and 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 in serum: LREFGuder WG, Narayanan S, Wisser H, et al. List of Analytes; Preanalytical Variables. Brochure in: Samples: From the Patient to the Laboratory. Darmstadt: GIT-Verlag 1996. | 2 days at 20‑25 °C |
7 days at 4‑8 °C | |
4 weeks at -20 °C |
Stability in EDTA/heparin plasma: LREFData on file at Roche Diagnostics. | 2 days at 15‑25 °C |
7 days at 2‑8 °C | |
4 weeks at (-15)‑(-25) °C |
In vitro test for the quantitative determination of creatine kinase (CK) in human serum and plasma on COBAS INTEGRA systems.
UV‑test
Creatine phosphate + ADP | CK | creatine + ATP |
ATP + D‑glucose | HK | ADP + G6P |
G6P + NADP+ | G6PDH | D‑6‑phosphogluconate + NADPH + H+ |
Equimolar quantities of NADPH and ATP are formed at the same rate. The photometrically measured rate of formation of NADPH is directly proportional to the CK activity.
Measuring range
7‑2000 U/L (0.12‑33.4 µkat/L)
Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:11 dilution. Results from samples diluted by the rerun function are automatically multiplied by a factor of 11.
Lower limits of measurement
Limit of Blank, Limit of Detection and Limit of Quantitation | |
Limit of Blank | = 7 U/L (0.12 µkat/L) |
Limit of Detection | = 7 U/L (0.12 µkat/L) |
Limit of Quantitation | = 7 U/L (0.12 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 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 precision of 20 % CV. It has been determined using low concentration creatine kinase samples.
Reference intervals strongly depend on the patient group and the specific clinical situation.
For healthy people, according to Klein et al.: LREFKlein G, Berger A, Bertholf R, et al. Abstract: Multicenter Evaluation of Liquid Reagents for CK, CK-MB and LDH with Determination of Reference Intervals on Hitachi Systems. Clin Chem 2001;47:Suppl. A30. | ||
CK | U/L | µkat/L |
Men | 39‑308 | 0.65‑5.14 |
Women | 26‑192 | 0.43‑3.21 |
Consensus values: LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308. | ||
CK | U/L | µkat/L |
Men | < 190 | < 3.20 |
Women | < 170 | < 2.85 |
Consensus values: LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308. | ||
CK‑MB | U/L | µkat/L |
Men/women | < 25 | < 0.42 |
Myocardial infarction: There is a high probability of myocardial damage when the following three conditions are fulfilled: LREFStein W. Strategie der klinischen-chemischen Diagnostik des frischen Myokardinfarktes. Med Welt 1985;36:572-577. | |||
U/L | µkat/L | ||
1 | CKmen | > 190 | > 3.17 |
CKwomen | > 167 | > 2.79 | |
2 | CK‑MB | > 24 | > 0.40 |
3 | The CK‑MB activity accounts for 6‑25 % of the total CK‑activity. |
According to Tietz: LREFWu AHB, editor. Tietz Clinical Guide to Laboratory Tests, 4th edition. St. Louis (MO): Saunders Elsevier 2006;306-307. | ||
CK | U/L | µkat/L |
Adult males > 19 years | 20‑200 | 0.33‑3.34 |
Adult females > 19 years | 20‑180 | 0.33‑3.01 |
The reference values according to Klein et al. are based on the 95th percentile of a group of healthy persons (202 men and 217 women) not involved in high‑intensity athletic activities.
In order to ensure high sensitivity in the diagnosis of heart diseases the values given by Tietz are recommended. The loss of diagnostic specificity thereby incurred can be compensated for by additionally determining CK‑MB and/or troponin T. When myocardial infarction is suspected the diagnostic strategy proposals in the consensus document of European and American cardiologists should in general be followed.
If despite the suspicion of myocardial infarction the values found remain below the stated limits, a fresh infarction may be involved. In such cases, the determinations should be repeated after 4 hours.
CK varies with physical activity level and race in healthy individuals.
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 a creatine kinase activity of 140 U/L (2.34 µkat/L).
Icterus:
Hemolysis:
Lipemia (Intralipid):
Drugs: No interference was found at therapeutic concentrations using common drug panels.
Cyanokit (Hydroxocobalamin) at therapeutic concentrations interferes with the test.
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 | ||
07190794190 | Creatine Kinase (200 tests) | System-ID 07 7485 5 | COBAS INTEGRA 400 plus |
10759350190 | Calibrator f.a.s. (12 x 3 mL) | System-ID 07 3718 6 | |
10759350360 | Calibrator f.a.s. (12 x 3 mL, for USA) | System-ID 07 3718 6 | |
12149435122 | Precinorm U plus (10 x 3 mL) | System-ID 07 7999 7 | |
12149435160 | Precinorm U plus (10 x 3 mL, for USA) | System-ID 07 7999 7 | |
12149443122 | Precipath U plus (10 x 3 mL) | System-ID 07 8000 6 | |
12149443160 | Precipath U plus (10 x 3 mL, for USA) | System-ID 07 8000 6 | |
05117003190 | PreciControl ClinChem Multi 1 (20 x 5 mL) | System-ID 07 7469 3 | |
05947626190 | PreciControl ClinChem Multi 1 (4 x 5 mL) | System-ID 07 7469 3 | |
05947626160 | PreciControl ClinChem Multi 1 (4 x 5 mL, for USA) | System-ID 07 7469 3 | |
05117216190 | PreciControl ClinChem Multi 2 (20 x 5 mL) | System-ID 07 7470 7 | |
05947774190 | PreciControl ClinChem Multi 2 (4 x 5 mL) | System-ID 07 7470 7 | |
05947774160 | PreciControl ClinChem Multi 2 (4 x 5 mL, for USA) | System-ID 07 7470 7 | |
20756350322 | NaCl Diluent 9 % (6 x 22 mL) | System-ID 07 5635 0 |
Test CK2, test ID 0-045
Ready for use
Measuring mode | Absorbance |
Abs. calculation mode | Kinsearch |
Reaction mode | R1‑S‑SR |
Reaction direction | Increase |
Wavelength A/B | 340/552 nm |
Calc. first/last | 10/45‑62 |
Unit | U/L |
Diluent (H2O) | ||
R1 | 100 µL | - |
Sample | 2.75 µL | 2 µL |
SR | 20 µL | - |
Total volume | 124.75 µL |
Shelf life at 2‑8 °C | See expiration date on cobas c pack label |
On-board in use at 10‑15 °C | 8 weeks |
Calibrator | Calibrator f.a.s. Use deionized water as zero calibrator. |
Calibration mode | Linear regression |
Calibration replicate | Duplicate recommended |
Calibration interval | Each lot and as required following quality control procedures |
Traceability: This method has been standardized against the IFCC Method for Creatine Kinase.
Representative performance data on the COBAS INTEGRA analyzers are given below. Results obtained in individual laboratories may differ.
Repeatability and intermediate precision were determined using human samples and controls in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP5 requirements (2 aliquots per run, 2 runs per day, 21 days). The following results were obtained:
Repeatability | Mean U/L (µkat/L) | SD U/L (µkat/L) | CV % |
|---|---|---|---|
Human serum 1 | 22.1 (0.37) | 0.9 (0.01) | 3.9 |
Human serum 2 | 144 (2.40) | 1.4 (0.02) | 1.0 |
Human serum 3 | 494 (8.25) | 4.6 (0.08) | 0.9 |
Human serum 4 | 980 (16.4) | 10 (0.2) | 1.0 |
Human serum 5 | 1893 (31.6) | 19 (0.3) | 1.0 |
PCCC Multi 1* | 162 (2.71) | 1.5 (0.03) | 0.9 |
PCCC Multi 2 | 311 (5.19) | 2.9 (0.05) | 0.9 |
Intermediate precision | Mean U/L (µkat/L) | SD U/L (µkat/L) | CV % |
|---|---|---|---|
Human serum 1 | 22.2 (0.37) | 1.0 (0.02) | 4.6 |
Human serum 2 | 145 (2.42) | 1.9 (0.03) | 1.3 |
Human serum 3 | 498 (8.31) | 5.7 (0.10) | 1.1 |
Human serum 4 | 980 (16.4) | 12 (0.19) | 1.2 |
Human serum 5 | 1893 (31.6) | 22 (0.36) | 1.1 |
PCCC Multi 1* | 161 (2.69) | 2.0 (0.03) | 1.3 |
PCCC Multi 2 | 309 (5.16) | 3.6 (0.06) | 1.2 |
*PCCC = PreciControl ClinChem
Creatine kinase values for human serum and plasma samples obtained on a COBAS INTEGRA 400 plus analyzer (y) were compared with those determined using the CKL reagent on a COBAS INTEGRA 800 analyzer (x).
Sample size (n) = 109
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 = 0.999x + 12.5 U/L | y = 0.987x + 19.7 U/L |
τ = 0.980 | r = 0.999 |
The sample activities were between 11.7 and 1819 U/L (0.20 and 30.4 µkat/L). |
Creatine kinase (CK) is a dimeric enzyme occurring in four different forms: a mitochondrial isoenzyme and the cytosolic isoenzymes CK‑MM (skeletal muscle type), CK‑BB (brain type) and CK‑MB (myocardial type).
The determination of CK and CK‑isoenzyme activities is utilized in the diagnosis and monitoring of myocardial infarction and myopathies such as the progressive Duchenne muscular dystrophy. Following injury to the myocardium, such as occurs with acute myocardial infarction
The assay method using creatine phosphate and ADP was first described by Oliver
Standardized methods for the determination of CK with activation by NAC were recommended by the German Society for Clinical Chemistry (DGKC)
R1 | Imidazole buffer: 123 mmol/L, pH 6.5 (37 °C); EDTA: 2.46 mmol/L; Mg2+: 12.3 mmol/L; ADP: 2.46 mmol/L; AMP: 6.14 mmol/L; diadenosine pentaphosphate: 19 µmol/L; NADP+ (yeast): 2.46 mmol/L; N‑acetylcysteine: 24.6 mmol/L; HK (yeast): ≥ 36.7 µkat/L; G6PDH (E. coli): ≥ 23.4 µkat/L; preservative; stabilizers; additives. |
SR | CAPSO* buffer: 20 mmol/L, pH 8.8 (37 °C); glucose: 120 mmol/L; EDTA: 2.46 mmol/L; creatine phosphate: 184 mmol/L; preservative; stabilizers. |
*CAPSO: 3‑(cyclohexylamine)‑2‑hydroxy‑1‑propanesulfonic acid |
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.
This kit contains components classified as follows in accordance with the Regulation (EC) No. 1272/2008:
H360D | May damage the unborn child. |
Prevention:
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P280 | Wear protective gloves/ protective clothing/ eye protection/ face protection/ hearing protection. |
Response:
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
Storage:
P405 | Store locked up. |
Disposal:
P501 | Dispose of contents/container to an approved waste disposal plant. |
Product safety labeling follows EU GHS guidance.
Contact phone: all countries: +49-621-7590, USA: 1-800-428-2336
Reference range | Precinorm U, Precinorm U plus, Precinorm CK‑MB or PreciControl ClinChem Multi 1 |
Pathological range | Precipath U, Precipath U plus, Precipath CK‑MB* or PreciControl ClinChem Multi 2 |
Control interval | 24 hours recommended |
Control sequence | User defined |
Control after calibration | Recommended |
*Not for use in the US
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: Nonhemolyzed serum is the specimen of choice and also recommended by IFCC.
Plasma: Li‑heparin, K2‑, K3‑EDTA plasma.
Please note: Differences in the degree of hemolysis resulting from the blood sampling procedure used can lead to deviating results in serum and 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 in serum: LREFGuder WG, Narayanan S, Wisser H, et al. List of Analytes; Preanalytical Variables. Brochure in: Samples: From the Patient to the Laboratory. Darmstadt: GIT-Verlag 1996. | 2 days at 20‑25 °C |
7 days at 4‑8 °C | |
4 weeks at -20 °C |
Stability in EDTA/heparin plasma: LREFData on file at Roche Diagnostics. | 2 days at 15‑25 °C |
7 days at 2‑8 °C | |
4 weeks at (-15)‑(-25) °C |
In vitro test for the quantitative determination of creatine kinase (CK) in human serum and plasma on Roche/Hitachi cobas c systems.
UV‑test
Creatine phosphate + ADP | CK | creatine + ATP |
ATP + D‑glucose | HK | ADP + G6P |
G6P + NADP+ | G6PDH | D‑6‑phosphogluconate + NADPH + H+ |
Equimolar quantities of NADPH and ATP are formed at the same rate. The photometrically measured rate of formation of NADPH is directly proportional to the CK activity.
7‑2000 U/L (0.12‑33.4 µkat/L)
Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:11 dilution. Results from samples diluted by the rerun function are automatically multiplied by a factor of 11.
Limit of Blank | = 7 U/L (0.12 µkat/L) |
Limit of Detection | = 7 U/L (0.12 µkat/L) |
Limit of Quantitation | = 7 U/L (0.12 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 creatine kinase samples.
Reference intervals strongly depend on the patient group and the specific clinical situation.
CK | Men | 39‑308 U/L |
Women | 26‑192 U/L |
CK | Men | < 190 U/L |
Women | < 170 U/L | |
CK‑MB | Men/women | < 25 U/L |
1 | CKmen | > 190 U/L |
CKwomen | > 167 U/L | |
2 | CK‑MB | > 24 U/L |
3 | The CK‑MB activity accounts for 6‑25 % of the total CK‑activity. |
CK | Adult males > 19 years | 20‑200 U/L |
Adult females > 19 years | 20‑180 U/L |
CK | Men | 0.65‑5.14 µkat/L |
Women | 0.43‑3.21 µkat/L | |
*calculated by unit conversion factor |
CK | Men | < 3.20 µkat/L |
Women | < 2.85 µkat/L | |
CK‑MB | Men/women | < 0.42 µkat/L |
1 | CKmen | > 3.17 µkat/L |
CKwomen | > 2.79 µkat/L | |
2 | CK‑MB | > 0.40 µkat/L |
3 | The CK‑MB activity accounts for 6‑25 % of the total CK‑activity. |
CK | Adult males > 19 years | 0.33‑3.34 µkat/L |
Adult females > 19 years | 0.33‑3.01 µkat/L | |
*calculated by unit conversion factor |
The reference values according to Klein et al. are based on the 95th percentile of a group of healthy persons (202 men and 217 women) not involved in high‑intensity athletic activities.
In order to ensure high sensitivity in the diagnosis of heart diseases the values given by Tietz are recommended. The loss of diagnostic specificity thereby incurred can be compensated for by additionally determining CK‑MB and/or troponin T. When myocardial infarction is suspected the diagnostic strategy proposals in the consensus document of European and American cardiologists should in general be followed.
If despite the suspicion of myocardial infarction the values found remain below the stated limits, a fresh infarction may be involved. In such cases, the determinations should be repeated after 4 hours.
CK varies with physical activity level and race in healthy individuals.
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 a creatine kinase activity of 140 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
|
| Analyzer(s) on which cobas c pack(s) can be used | |
08057460190 | Creatine Kinase (500 tests) | System-ID 2042 001 | |
10759350360 | Calibrator f.a.s. (12 x 3 mL) | Code 20401 | |
05947626160 | PreciControl ClinChem Multi 1 (4 x 5 mL) | Code 20391 | |
05947774160 | PreciControl ClinChem Multi 2 (4 x 5 mL) | Code 20392 | |
08063494190 | Diluent NaCl 9 % (123 mL) | System-ID 2906 001 |
CK2: ACN 20420
Ready for use
Reporting time | 10 min | ||
Wavelength (sub/main) | 546/340 nm | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 79 µL | – | |
R3 | 16 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 2.2 µL | – | – |
Decreased | 2.2 µL | 10 µL | 100 µL |
Increased | 2.2 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: | 8 weeks |
Calibrators | S1: H2O S2: C.f.a.s. |
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 method has been standardized against the IFCC Method for Creatine Kinase.
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) | 155 | 0.764 | 0.5 |
PCCC2b) | 287 | 0.988 | 0.3 |
Human serum 1 | 19.5 | 0.524 | 2.7 |
Human serum 2 | 85.7 | 0.510 | 0.6 |
Human serum 3 | 176 | 1.12 | 0.6 |
Human serum 4 | 900 | 3.28 | 0.4 |
Human serum 5 | 1588 | 4.52 | 0.3 |
Intermediate precision | Mean | SD | CV |
PCCC1 FREFPreciControl ClinChem Multi 1 | 155 | 1.04 | 0.7 |
PCCC2 FREFPreciControl ClinChem Multi 2 | 287 | 2.02 | 0.7 |
Human serum 1 | 19.4 | 0.582 | 3.0 |
Human serum 2 | 85.7 | 1.01 | 1.2 |
Human serum 3 | 176 | 1.96 | 1.1 |
Human serum 4 | 895 | 10.7 | 1.2 |
Human serum 5 | 1588 | 18.7 | 1.2 |
Creatine kinase values for human serum and plasma samples obtained on a
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 = 0.988x + 1.20 U/L | y = 0.993x − 0.788 U/L |
τ = 0.996 | r = 1.000 |
The sample activities were between 8.20 and 1938 U/L.
Creatine kinase 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 = 1.006x + 0.553 U/L | y = 1.013x − 1.03 U/L |
τ = 0.990 | r = 1.000 |
The sample activites were between 11.0 and 1959 U/L.
Creatine kinase (CK) is a dimeric enzyme occurring in four different forms: a mitochondrial isoenzyme and the cytosolic isoenzymes CK‑MM (skeletal muscle type), CK‑BB (brain type) and CK‑MB (myocardial type).
The determination of CK and CK‑isoenzyme activities is utilized in the diagnosis and monitoring of myocardial infarction and myopathies such as the progressive Duchenne muscular dystrophy. Following injury to the myocardium, such as occurs with acute myocardial infarction
The assay method using creatine phosphate and ADP was first described by Oliver
Standardized methods for the determination of CK with activation by NAC were recommended by the German Society for Clinical Chemistry (DGKC)
R1 | Imidazole buffer: 123 mmol/L, pH 6.5 (37 °C); EDTA: 2.46 mmol/L; Mg2+: 12.3 mmol/L; ADP: 2.46 mmol/L; AMP: 6.14 mmol/L; diadenosine pentaphosphate: 19 µmol/L; NADP+ (yeast): 2.46 mmol/L; N‑acetylcysteine: 24.6 mmol/L; HK (yeast): ≥ 36.7 µkat/L; G6PDH (E. coli): ≥ 23.4 µkat/L; preservative; stabilizers; additives. |
R3 | CAPSO* buffer: 20 mmol/L, pH 8.8 (37 °C); glucose: 120 mmol/L; EDTA: 2.46 mmol/L; creatine phosphate: 184 mmol/L; preservative; stabilizers. |
*CAPSO: 3‑(cyclohexylamine)‑2‑hydroxy‑1‑propanesulfonic acid |
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.
This kit contains components classified as follows in accordance with the Regulation (EC) No. 1272/2008:
For USA: Caution: Federal law restricts this device to sale by or on the order of a physician.
H360D | May damage the unborn child. |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P280 | Wear protective gloves/ protective clothing/ eye protection/ face protection/ hearing protection. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P405 | Store locked up. |
P501 | Dispose of contents/container to an approved waste disposal plant. |
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 8 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: Nonhemolyzed serum is the specimen of choice and also recommended by IFCC.
Plasma: Li‑heparin, K2‑, K3‑EDTA plasma.
Please note: Differences in the degree of hemolysis resulting from the blood sampling procedure used can lead to deviating results in serum and 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 in serum: LREFGuder WG, Narayanan S, Wisser H, et al. List of Analytes; Preanalytical Variables. Brochure in: Samples: From the Patient to the Laboratory. Darmstadt: GIT-Verlag 1996. | 2 days at 20‑25 °C 7 days at 4‑8 °C 4 weeks at -20 °C |
Stability in EDTA/heparin plasma: | 2 days at 15‑25 °C 7 days at 2‑8 °C 4 weeks 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 creatine kinase (CK) in human serum and plasma on
UV‑test
Creatine phosphate + ADP | CK | creatine + ATP |
ATP + D‑glucose | HK | ADP + G6P |
G6P + NADP+ | G6PDH | D‑6‑phosphogluconate + NADPH + H+ |
Equimolar quantities of NADPH and ATP are formed at the same rate. The photometrically measured rate of formation of NADPH is directly proportional to the CK activity.
7‑2000 U/L (0.12‑33.4 µkat/L)
Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:11 dilution. Results from samples diluted by the rerun function are automatically multiplied by a factor of 11.
Limit of Blank | = 7 U/L (0.12 µkat/L) |
Limit of Detection | = 7 U/L (0.12 µkat/L) |
Limit of Quantitation | = 7 U/L (0.12 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 creatine kinase samples.
Reference intervals strongly depend on the patient group and the specific clinical situation.
CK | Men | 39‑308 U/L |
Women | 26‑192 U/L |
CK | Men | < 190 U/L |
Women | < 170 U/L | |
CK‑MB | Men/women | < 25 U/L |
1 | CKmen | > 190 U/L |
CKwomen | > 167 U/L | |
2 | CK‑MB | > 24 U/L |
3 | The CK‑MB activity accounts for 6‑25 % of the total CK‑activity. |
CK | Adult males > 19 years | 20‑200 U/L |
Adult females > 19 years | 20‑180 U/L |
CK | Men | 0.65‑5.14 µkat/L |
Women | 0.43‑3.21 µkat/L | |
*calculated by unit conversion factor |
CK | Men | < 3.20 µkat/L |
Women | < 2.85 µkat/L | |
CK‑MB | Men/women | < 0.42 µkat/L |
1 | CKmen | > 3.17 µkat/L |
CKwomen | > 2.79 µkat/L | |
2 | CK‑MB | > 0.40 µkat/L |
3 | The CK‑MB activity accounts for 6‑25 % of the total CK‑activity. |
CK | Adult males > 19 years | 0.33‑3.34 µkat/L |
Adult females > 19 years | 0.33‑3.01 µkat/L | |
*calculated by unit conversion factor |
The reference values according to Klein et al. are based on the 95th percentile of a group of healthy persons (202 men and 217 women) not involved in high‑intensity athletic activities.
In order to ensure high sensitivity in the diagnosis of heart diseases the values given by Tietz are recommended. The loss of diagnostic specificity thereby incurred can be compensated for by additionally determining CK‑MB and/or troponin T. When myocardial infarction is suspected the diagnostic strategy proposals in the consensus document of European and American cardiologists should in general be followed.
If despite the suspicion of myocardial infarction the values found remain below the stated limits, a fresh infarction may be involved. In such cases, the determinations should be repeated after 4 hours.
CK varies with physical activity level and race in healthy individuals.
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 a creatine kinase activity of 140 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 | |||
08057460190 | Creatine Kinase (500 tests) | System-ID 2042 001 | cobas c 303, cobas c 503 |
Materials required (but not provided):
10759350190 | Calibrator f.a.s. (12 x 3 mL) | Code 20401 | |
05117003190 | PreciControl ClinChem Multi 1 (20 x 5 mL) | Code 20391 | |
05947626190 | PreciControl ClinChem Multi 1 (4 x 5 mL) | Code 20391 | |
05117216190 | PreciControl ClinChem Multi 2 (20 x 5 mL) | Code 20392 | |
05947774190 | PreciControl ClinChem Multi 2 (4 x 5 mL) | Code 20392 | |
08063494190 | Diluent NaCl 9 % (123 mL) | System-ID 2906 001 |
CK2: ACN 20420
Ready for use
Reporting time | 10 min | ||
Wavelength (sub/main) | 546/340 nm | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 79 µL | – | |
R3 | 16 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 2.2 µL | – | – |
Decreased | 2.2 µL | 10 µL | 100 µL |
Increased | 2.2 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: | 8 weeks |
Calibrators | S1: H2O S2: C.f.a.s. |
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 method has been standardized against the IFCC Method for Creatine Kinase.
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). Results for repeatability and intermediate precision were obtained on the cobas c 503 analyzer.
Repeatability | Mean | SD | CV |
PCCC1a) | 155 | 0.764 | 0.5 |
PCCC2b) | 287 | 0.988 | 0.3 |
Human serum 1 | 19.5 | 0.524 | 2.7 |
Human serum 2 | 85.7 | 0.510 | 0.6 |
Human serum 3 | 176 | 1.12 | 0.6 |
Human serum 4 | 900 | 3.28 | 0.4 |
Human serum 5 | 1588 | 4.52 | 0.3 |
Intermediate precision | Mean | SD | CV |
PCCC1 FREFPreciControl ClinChem Multi 1 | 155 | 1.04 | 0.7 |
PCCC2 FREFPreciControl ClinChem Multi 2 | 287 | 2.02 | 0.7 |
Human serum 1 | 19.4 | 0.582 | 3.0 |
Human serum 2 | 85.7 | 1.01 | 1.2 |
Human serum 3 | 176 | 1.96 | 1.1 |
Human serum 4 | 895 | 10.7 | 1.2 |
Human serum 5 | 1588 | 18.7 | 1.2 |
The data obtained on cobas c 503 analyzer(s) are representative for cobas c 303 analyzer(s).
Creatine kinase 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 = 0.988x + 1.20 U/L | y = 0.993x − 0.788 U/L |
τ = 0.996 | r = 1.000 |
The sample activities were between 8.20 and 1938 U/L.
Creatine kinase 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 = 1.006x + 0.553 U/L | y = 1.013x − 1.03 U/L |
τ = 0.990 | r = 1.000 |
The sample activities were between 11.0 and 1959 U/L.
Creatine kinase (CK) is a dimeric enzyme occurring in four different forms: a mitochondrial isoenzyme and the cytosolic isoenzymes CK‑MM (skeletal muscle type), CK‑BB (brain type) and CK‑MB (myocardial type).
The determination of CK and CK‑isoenzyme activities is utilized in the diagnosis and monitoring of myocardial infarction and myopathies such as the progressive Duchenne muscular dystrophy. Following injury to the myocardium, such as occurs with acute myocardial infarction
The assay method using creatine phosphate and ADP was first described by Oliver
Standardized methods for the determination of CK with activation by NAC were recommended by the German Society for Clinical Chemistry (DGKC)
R1 | Imidazole buffer: 123 mmol/L, pH 6.5 (37 °C); EDTA: 2.46 mmol/L; Mg2+: 12.3 mmol/L; ADP: 2.46 mmol/L; AMP: 6.14 mmol/L; diadenosine pentaphosphate: 19 µmol/L; NADP+ (yeast): 2.46 mmol/L; N‑acetylcysteine: 24.6 mmol/L; HK (yeast): ≥ 36.7 µkat/L; G6PDH (E. coli): ≥ 23.4 µkat/L; preservative; stabilizers; additives. |
R3 | CAPSO* buffer: 20 mmol/L, pH 8.8 (37 °C); glucose: 120 mmol/L; EDTA: 2.46 mmol/L; creatine phosphate: 184 mmol/L; preservative; stabilizers. |
*CAPSO: 3‑(cyclohexylamine)‑2‑hydroxy‑1‑propanesulfonic acid |
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.
This kit contains components classified as follows in accordance with the Regulation (EC) No. 1272/2008:
H360D | May damage the unborn child. |
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P280 | Wear protective gloves/ protective clothing/ eye protection/ face protection/ hearing protection. |
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
P405 | Store locked up. |
P501 | Dispose of contents/container to an approved waste disposal plant. |
Product safety labeling follows EU GHS guidance.
Contact phone: all countries: +49-621-7590
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 8 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: Nonhemolyzed serum is the specimen of choice and also recommended by IFCC.
Plasma: Li‑heparin, K2‑, K3‑EDTA plasma.
Please note: Differences in the degree of hemolysis resulting from the blood sampling procedure used can lead to deviating results in serum and 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 in serum: LREFGuder WG, Narayanan S, Wisser H, et al. List of Analytes; Preanalytical Variables. Brochure in: Samples: From the Patient to the Laboratory. Darmstadt: GIT-Verlag 1996. | 2 days at 20‑25 °C 7 days at 4‑8 °C 4 weeks at -20 °C |
Stability in EDTA/heparin plasma: | 2 days at 15‑25 °C 7 days at 2‑8 °C 4 weeks 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 creatine kinase (CK) in human serum and plasma on the cobas c 111 system.
UV‑test
Creatine phosphate + ADP | CK | creatine + ATP |
ATP + D‑glucose | HK | ADP + G6P |
G6P + NADP+ | G6PDH | D‑6‑phosphogluconate + NADPH + H+ |
Equimolar quantities of NADPH and ATP are formed at the same rate. The photometrically measured rate of formation of NADPH is directly proportional to the CK activity.
Measuring range
7‑2000 U/L (0.12‑33.4 µkat/L)
Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:11 dilution. Results from samples diluted by the rerun function are automatically multiplied by a factor of 11.
Lower limits of measurement
Limit of Blank, Limit of Detection and Limit of Quantitation | |
Limit of Blank | = 7 U/L (0.12 µkat/L) |
Limit of Detection | = 7 U/L (0.12 µkat/L) |
Limit of Quantitation | = 7 U/L (0.12 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 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 precision of 20 % CV. It has been determined using low concentration creatine kinase samples.
Reference intervals strongly depend on the patient group and the specific clinical situation.
For healthy people, according to Klein et al.: LREFKlein G, Berger A, Bertholf R, et al. Abstract: Multicenter Evaluation of Liquid Reagents for CK, CK-MB and LDH with Determination of Reference Intervals on Hitachi Systems. Clin Chem 2001;47:Suppl. A30. | ||
CK | U/L | µkat/L |
Men | 39‑308 | 0.65‑5.14 |
Women | 26‑192 | 0.43‑3.21 |
Consensus values: LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308. | ||
CK | U/L | µkat/L |
Men | < 190 | < 3.20 |
Women | < 170 | < 2.85 |
Consensus values: LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308. | ||
CK‑MB | U/L | µkat/L |
Men/women | < 25 | < 0.42 |
Myocardial infarction: There is a high probability of myocardial damage when the following three conditions are fulfilled: LREFStein W. Strategie der klinischen-chemischen Diagnostik des frischen Myokardinfarktes. Med Welt 1985;36:572-577. | |||
U/L | µkat/L | ||
1 | CKmen | > 190 | > 3.17 |
CKwomen | > 167 | > 2.79 | |
2 | CK‑MB | > 24 | > 0.40 |
3 | The CK‑MB activity accounts for 6‑25 % of the total CK‑activity. |
According to Tietz: LREFWu AHB, editor. Tietz Clinical Guide to Laboratory Tests, 4th edition. St. Louis (MO): Saunders Elsevier 2006;306-307. | ||
CK | U/L | µkat/L |
Adult males > 19 years | 20‑200 | 0.33‑3.34 |
Adult females > 19 years | 20‑180 | 0.33‑3.01 |
The reference values according to Klein et al. are based on the 95th percentile of a group of healthy persons (202 men and 217 women) not involved in high‑intensity athletic activities.
In order to ensure high sensitivity in the diagnosis of heart diseases the values given by Tietz are recommended. The loss of diagnostic specificity thereby incurred can be compensated for by additionally determining CK‑MB and/or troponin T. When myocardial infarction is suspected the diagnostic strategy proposals in the consensus document of European and American cardiologists should in general be followed.
If despite the suspicion of myocardial infarction the values found remain below the stated limits, a fresh infarction may be involved. In such cases, the determinations should be repeated after 4 hours.
CK varies with physical activity level and race in healthy individuals.
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 a creatine kinase activity of 140 U/L (2.34 µkat/L).
Icterus:
Hemolysis:
Lipemia (Intralipid):
Drugs: No interference was found at therapeutic concentrations using common drug panels.
Cyanokit (Hydroxocobalamin) at therapeutic concentrations interferes with the test.
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 the cobas c 111 analyzer. For information about test combinations requiring special wash steps, please refer to the latest version of the carry-over evasion list found with the CLEAN Method Sheet and the operator’s manual for further instructions.
Where required, special wash/carry-over evasion programming must be implemented prior to reporting results with this test.
|
| Analyzer(s) on which kit(s) can be used | |
07442017190 | Creatine Kinase (2 x 100 tests) | cobas c 111 |
10759350190 | Calibrator f.a.s. (12 x 3 mL) | Code 401 | |
10759350360 | Calibrator f.a.s. (12 x 3 mL, for USA) | Code 401 | |
12149435122 | Precinorm U plus (10 x 3 mL) | Code 300 | |
12149435160 | Precinorm U plus (10 x 3 mL, for USA) | Code 300 | |
12149443122 | Precipath U plus (10 x 3 mL) | Code 301 | |
12149443160 | Precipath U plus (10 x 3 mL, for USA) | Code 301 | |
05117003190 | PreciControl ClinChem Multi 1 (20 x 5 mL) | Code 391 | |
05947626190 | PreciControl ClinChem Multi 1 (4 x 5 mL) | Code 391 | |
05947626160 | PreciControl ClinChem Multi 1 (4 x 5 mL, for USA) | Code 391 | |
05117216190 | PreciControl ClinChem Multi 2 (20 x 5 mL) | Code 392 | |
05947774190 | PreciControl ClinChem Multi 2 (4 x 5 mL) | Code 392 | |
05947774160 | PreciControl ClinChem Multi 2 (4 x 5 mL, for USA) | Code 392 | |
04774230190 | NaCl Diluent 9 % (4 x 12 mL) | Code 951 |
CK2: ACN 550
Ready for use
Measuring mode | Absorbance |
Abs. calculation mode | Kinetic |
Reaction direction | Increase |
Wavelength A/B | 340/552 nm |
Calc. first/last | 24-34 |
Unit | U/L (µkat/L) |
Reaction mode | R1-S-SR |
Diluent (H2O) | ||
R1 | 100 µL | - |
Sample | 2.75 µL | 2 µL |
SR | 20 µL | - |
Total volume | 124.75 µL |
Shelf life at 2‑8 °C: | See expiration date on reagent |
On-board in use and refrigerated on the analyzer: | 4 weeks |
Shelf life at 2‑8 °C: | See expiration date on reagent |
On-board in use and refrigerated on the analyzer: | 4 weeks |
Calibrators | Calibrator f.a.s. |
Calibration mode | Linear regression |
Calibration interval | Each lot and as required following quality control procedures. |
Traceability: This method has been standardized against the IFCC Method for Creatine Kinase.
Representative performance data on the cobas c 111 analyzer are given below. Results obtained in individual laboratories may differ.
Repeatability and intermediate precision were determined using human samples and controls in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP5 requirements (2 aliquots per run, 2 runs per day, 21 days). The following results were obtained:
Repeatability | Mean U/L (µkat/L) | SD U/L (µkat/L) | CV % |
|---|---|---|---|
Human serum 1 | 94.6 (1.58) | 1.0 (0.02) | 1.1 |
Human serum 2 | 141 (2.35) | 1.2 (0.02) | 0.9 |
Human serum 3 | 320 (5.34) | 2.7 (0.05) | 0.9 |
Human serum 4 | 964 (16.1) | 9.1 (0.15) | 0.9 |
Human serum 5 | 1771 (29.6) | 11 (0.18) | 0.6 |
PCCC Multi 1* | 149 (2.49) | 1.4 (0.02) | 1.0 |
PCCC Multi 2 | 273 (4.56) | 4.0 (0.07) | 1.5 |
Intermediate precision | Mean U/L (µkat/L) | SD U/L (µkat/L) | CV % |
|---|---|---|---|
Human serum 1 | 94.6 (1.58) | 1.7 (0.03) | 1.8 |
Human serum 2 | 141 (2.35) | 2.2 (0.04) | 1.5 |
Human serum 3 | 320 (5.34) | 4.9 (0.08) | 1.5 |
Human serum 4 | 964 (16.1) | 22 (0.37) | 2.2 |
Human serum 5 | 1771 (29.6) | 24 (0.40) | 1.4 |
PCCC Multi 1 | 149 (2.49) | 1.7 (0.03) | 1.2 |
PCCC Multi 2 | 273 (4.56) | 4.0 (0.07) | 1.5 |
*PCCC = PreciControl ClinChem
Creatine kinase values for human serum and plasma samples obtained on the cobas c 111 analyzer (y) were compared with those determined using the corresponding reagent on a COBAS INTEGRA 400 plus analyzer (x).
Sample size (n) = 65
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 = 0.972x + 10.4 U/L | y = 0.956x + 21.1 U/L |
τ = 0.992 | r = 0.999 |
The sample activities were between 7.7 and 1815 U/L (0.13 and 30.3 µkat/L). |
Creatine kinase (CK) is a dimeric enzyme occurring in four different forms: a mitochondrial isoenzyme and the cytosolic isoenzymes CK‑MM (skeletal muscle type), CK‑BB (brain type) and CK‑MB (myocardial type).
The determination of CK and CK‑isoenzyme activities is utilized in the diagnosis and monitoring of myocardial infarction and myopathies such as the progressive Duchenne muscular dystrophy. Following injury to the myocardium, such as occurs with acute myocardial infarction,
The assay method using creatine phosphate and ADP was first described by Oliver,
Standardized methods for the determination of CK with activation by NAC were recommended by the German Society for Clinical Chemistry (DGKC)
R1 | Imidazole buffer: 123 mmol/L, pH 6.5 (37 °C); EDTA: 2.46 mmol/L; Mg2+: 12.3 mmol/L; ADP: 2.46 mmol/L; AMP: 6.14 mmol/L; diadenosine pentaphosphate: 19 µmol/L; NADP+ (yeast): 2.46 mmol/L; N‑acetylcysteine: 24.6 mmol/L; HK (yeast): ≥ 36.7 µkat/L; G6PDH (E. coli): ≥ 23.4 µkat/L; preservative; stabilizers; additives. |
SR | CAPSO* buffer: 20 mmol/L, pH 8.8 (37 °C); glucose: 120 mmol/L; EDTA: 2.46 mmol/L; creatine phosphate: 184 mmol/L; preservative; stabilizers. |
*CAPSO: 3‑(cyclohexylamine)‑2‑hydroxy‑1‑propanesulfonic acid |
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:
H360D | May damage the unborn child. |
Prevention:
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P280 | Wear protective gloves/ protective clothing/ eye protection/ face protection/ hearing protection. |
Response:
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
Storage:
P405 | Store locked up. |
Disposal:
P501 | Dispose of contents/container to an approved waste disposal plant. |
Product safety labeling follows EU GHS guidance.
Contact phone: all countries: +49-621-7590, USA: 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. 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: Nonhemolyzed serum is the specimen of choice and also recommended by IFCC.
Plasma: Li‑Heparin, K2‑, K3‑EDTA plasma.
Please note: Differences in the degree of hemolysis resulting from the blood sampling procedure used can lead to deviating results in serum and 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 in serum: LREFGuder WG, Narayanan S, Wisser H, et al. List of Analytes; Preanalytical Variables. Brochure in: Samples: From the Patient to the Laboratory. Darmstadt: GIT-Verlag 1996. | 2 days at 20‑25 °C |
7 days at 4‑8 °C | |
4 weeks at -20 °C |
Stability in EDTA/heparin plasma: LREFData on file at Roche Diagnostics. | 2 days at 15‑25 °C |
7 days at 2‑8 °C | |
4 weeks at (-15)‑(-25) °C |
In vitro test for the quantitative determination of creatine kinase (CK) in human serum and plasma on
UV‑test
Creatine phosphate + ADP | CK | creatine + ATP |
ATP + D‑glucose | HK | ADP + G6P |
G6P + NADP+ | G6PDH | D‑6‑phosphogluconate + NADPH + H+ |
Equimolar quantities of NADPH and ATP are formed at the same rate. The photometrically measured rate of formation of NADPH is directly proportional to the CK activity.
Measuring range
7‑2000 U/L (0.117‑33.4 µkat/L)
Determine samples having higher activities via the rerun function. Dilution of samples via the rerun function is a 1:11 dilution. Results from samples diluted using the rerun function are automatically multiplied by a factor of 11.
Lower limits of measurement
Lower detection limit of the test
7 U/L (0.12 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 (< 7 U/L) will not be flagged by the instrument.
Reference intervals strongly depend on the patient group and the specific clinical situation.
For healthy people, according to Klein et al.: LREFKlein G, Berger A, Bertholf R, et al. Abstract: Multicenter Evaluation of Liquid Reagents for CK, CK-MB and LDH with Determination of Reference Intervals on Hitachi Systems. Clin Chem 2001;47:Suppl. A30. | ||
CK | U/L | µkat/L |
Men | 39‑308 | 0.65‑5.14 |
Women | 26‑192 | 0.43‑3.21 |
Consensus values: LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308. | ||
CK | U/L | µkat/L |
Men | < 190 | < 3.20 |
Women | < 170 | < 2.85 |
Consensus values: LREFThomas L, Müller M, Schumann G, et al. Consensus of DGKL and VDGH for interim reference intervals on enzymes in serum. J Lab Med 2005; 29(5):301-308. | ||
CK‑MB | U/L | µkat/L |
Men/women | < 25 | < 0.42 |
Myocardial infarction: There is a high probability of myocardial damage when the following three conditions are fulfilled: LREFStein W. Strategie der klinischen-chemischen Diagnostik des frischen Myokardinfarktes. Med Welt 1985;36:572-577. | |||
U/L | µkat/L | ||
1 | CKmen | > 190 | > 3.17 |
CKwomen | > 167 | > 2.79 | |
2 | CK‑MB | > 24 | > 0.40 |
3 | The CK‑MB activity accounts for 6‑25 % of the total CK‑activity. |
According to Tietz: LREFWu AHB, editor. Tietz Clinical Guide to Laboratory Tests, 4th edition. St. Louis (MO): Saunders Elsevier 2006;306-307. | ||
CK | U/L | µkat/L |
Adult males > 19 years | 20‑200 | 0.33‑3.34 |
Adult females > 19 years | 20‑180 | 0.33‑3.01 |
The reference values according to Klein et al. are based on the 95th percentile of a group of healthy persons (202 men and 217 women) not involved in high‑intensity athletic activities.
In order to ensure high sensitivity in the diagnosis of heart diseases the values given by Tietz are recommended. The loss of diagnostic specificity thereby incurred can be compensated for by additionally determining CK‑MB and/or troponin T. When myocardial infarction is suspected the diagnostic strategy proposals in the consensus document of European and American cardiologists should in general be followed.
If despite the suspicion of myocardial infarction the values found remain below the stated limits, a fresh infarction may be involved. In such cases, the determinations should be repeated after 4 hours.
CK varies with physical activity level and race in healthy individuals.
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 a creatine kinase activity of 140 U/L (2.34 µkat/L).
Icterus:
Hemolysis:
Lipemia (Intralipid):
Drugs: No interference was found at therapeutic concentrations using common drug panels.
Cyanokit (Hydroxocobalamin) at therapeutic concentrations interferes with the test.
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, 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 | |
05168546190* | Creatine Kinase (800 tests) | System-ID 03 5923 6 | |
05168546214* | Creatine Kinase (800 tests) | System-ID 03 5923 6 | cobas c 701/702 |
10759350190 | Calibrator f.a.s. (12 x 3 mL) | Code 401 | |
10759350360 | Calibrator f.a.s. (12 x 3 mL, for USA) | Code 401 | |
12149435122 | Precinorm U plus (10 x 3 mL) | Code 300 | |
12149435160 | Precinorm U plus (10 x 3 mL, for USA) | Code 300 | |
12149443122 | Precipath U plus (10 x 3 mL) | Code 301 | |
12149443160 | Precipath U plus (10 x 3 mL, for USA) | Code 301 | |
05117003190 | PreciControl ClinChem Multi 1 (20 x 5 mL) | Code 391 | |
05947626190 | PreciControl ClinChem Multi 1 (4 x 5 mL) | Code 391 | |
05947626160 | PreciControl ClinChem Multi 1 (4 x 5 mL, for USA) | Code 391 | |
05117216190 | PreciControl ClinChem Multi 2 (20 x 5 mL) | Code 392 | |
05947774190 | PreciControl ClinChem Multi 2 (4 x 5 mL) | Code 392 | |
05947774160 | PreciControl ClinChem Multi 2 (4 x 5 mL, for USA) | Code 392 | |
05172152190 | Diluent NaCl 9 % (119 mL) | System-ID 08 6869 3 |
* Some kits shown may not be available in all countries.
CK: ACN 8057
CK2: ACN 8550
Ready for use
cobas c 701/702 test definition | |||
Assay type | Rate A | ||
Reaction time / Assay points | 10 / 27‑38 | ||
Wavelength (sub/main) | 546/340 nm | ||
Reaction direction | Increase | ||
Units | U/L (µkat/L) | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 100 µL | – | |
R3 | 20 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 2.8 µL | – | – |
Decreased | 2.8 µL | 15 µL | 150 µL |
Increased | 5.6 µL | – | – |
CK | |
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 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 method has been standardized against the IFCC Method for Creatine Kinase.
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 | 148 (2.47) | 1 (0.02) | 0.7 |
Precipath U | 479 (8.00) | 2 (0.03) | 0.5 |
Human serum A | 73.3 (1.22) | 0.4 (0.01) | 0.5 |
Human serum B | 744 (12.4) | 4 (0.1) | 0.5 |
Human serum C | 1990 (33.2) | 11 (0.2) | 0.5 |
Intermediate precision | Mean U/L (µkat/L) | SD U/L (µkat/L) | CV % |
Precinorm U | 160 (2.67) | 1.1 (0.02) | 0.7 |
Precipath U | 492 (8.20) | 1.7 (0.03) | 0.4 |
Human serum 1 | 183 (3.05) | 2.5 (0.04) | 1.4 |
Results for intermediate precision were obtained on the Roche/Hitachi 917 analyzer.
Creatine kinase values for human serum and plasma samples obtained on a
Sample size (n) = 176
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 = 0.992x + 0.640 U/L | y = 0.999x - 1.25 U/L |
τ = 0.991 | r = 1.000 |
The sample activities were between 8.20 and 1953 U/L (0.137 and 32.6 µkat/L). |
Creatine kinase (CK) is a dimeric enzyme occurring in four different forms: a mitochondrial isoenzyme and the cytosolic isoenzymes CK‑MM (skeletal muscle type), CK‑BB (brain type) and CK‑MB (myocardial type).
The determination of CK and CK‑isoenzyme activities is utilized in the diagnosis and monitoring of myocardial infarction and myopathies such as the progressive Duchenne muscular dystrophy. Following injury to the myocardium, such as occurs with acute myocardial infarction
The assay method using creatine phosphate and ADP was first described by Oliver
Standardized methods for the determination of CK with activation by NAC were recommended by the German Society for Clinical Chemistry (DGKC)
R1 | Imidazole buffer: 123 mmol/L, pH 6.5 (37 °C); EDTA: 2.46 mmol/L; Mg2+: 12.3 mmol/L; ADP: 2.46 mmol/L; AMP: 6.14 mmol/L; diadenosine pentaphosphate: 19 µmol/L; NADP+ (yeast): 2.46 mmol/L; N‑acetylcysteine: 24.6 mmol/L; HK (yeast): ≥ 36.7 µkat/L; G6PDH (E. coli): ≥ 23.4 µkat/L; preservative; stabilizers; additives. |
R3 | CAPSO* buffer: 20 mmol/L, pH 8.8 (37 °C); glucose: 120 mmol/L; EDTA: 2.46 mmol/L; creatine phosphate: 184 mmol/L; preservative; stabilizers. |
*CAPSO: 3(‑cyclohexylamine)‑2‑hydroxy‑1‑propanesulfonic acid |
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.
This kit contains components classified as follows in accordance with the Regulation (EC) No. 1272/2008:
H360D | May damage the unborn child. |
Prevention:
P201 | Obtain special instructions before use. |
P202 | Do not handle until all safety precautions have been read and understood. |
P280 | Wear protective gloves/ protective clothing/ eye protection/ face protection/ hearing protection. |
Response:
P308 + P313 | IF exposed or concerned: Get medical advice/attention. |
Storage:
P405 | Store locked up. |
Disposal:
P501 | Dispose of contents/container to an approved waste disposal plant. |
Product safety labeling follows EU GHS guidance.
Contact phone: all countries: +49-621-7590, USA: 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. 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: Nonhemolyzed serum is the specimen of choice and also recommended by IFCC.
Plasma: Li‑Heparin, K2‑, K3‑EDTA plasma.
Please note: Differences in the degree of hemolysis resulting from the blood sampling procedure used can lead to deviating results in serum and 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 in serum: LREFGuder WG, Narayanan S, Wisser H, et al. List of Analytes; Preanalytical Variables. Brochure in: Samples: From the Patient to the Laboratory. Darmstadt: GIT-Verlag 1996. | 2 days at 20‑25 °C |
7 days at 4‑8 °C | |
4 weeks at -20 °C |
Stability in EDTA/heparin plasma: | 2 days at 15‑25 °C |
7 days at 2‑8 °C | |
4 weeks at (-15)‑(-25) °C |
![](\"http://pim-media.roche.com/Images/REF_Frame_1_970150539_All.jpg\"/)
![](\"http://pim-media.roche.com/Images/CONTENT_Frame_1_970070027_All.jpg\"/)