In vitro test for the quantitative determination of amikacin in serum and plasma on Roche/Hitachi cobas c systems.
Kinetic interaction of microparticles in solution (KIMS) as measured by changes in light transmission.
The assay is a homogeneous immunoassay based on the principle of measuring changes in scattered light or absorbance which result when activated microparticles aggregate. The microparticles are coated with amikacin and rapidly aggregate in the presence of an amikacin antibody solution. When a sample containing amikacin is introduced, the aggregation reaction is partially inhibited, slowing the rate of the aggregation process. Antibody bound to sample drug is no longer available to promote microparticle aggregation, and subsequent particle lattice formation is inhibited. Thus, a classic inhibition curve with respect to amikacin concentration is obtained, with the maximum rate of aggregation at the lowest amikacin concentration. By monitoring the change in scattered light or absorbance, a concentration-dependent curve is obtained.
0.8‑40 µg/mL (1.4‑68.4 µmol/L)
Manually dilute samples above the measuring range 1 + 1 with the Preciset TDM II Diluent (0 µg/mL) and reassay. Multiply the result by 2 to obtain the specimen value.
Lower limits of measurement
Lower detection limit of the test:
0.8 µg/mL (1.4 µmol/L)
The lower detection limit represents the lowest measurable analyte level that can be distinguished from zero. It is calculated as the value lying 2 standard deviations above that of the 0 μg/mL calibrator (standard 1 + 2 SD, repeatability, n = 21).
Values below the lower detection limit (< 0.8 µg/mL) will not be flagged by the instrument.
Although optimum values may vary, peak serum values of amikacin in the range of 20 to 25 µg/mL (34.2 to 42.8 µmol/L) and trough values in the range of 5 to 10 µg/mL (8.6 to 17.1 µmol/L) are generally accepted for therapeutic effectiveness. Toxicity is associated with peak levels greater than 35 µg/mL (59.9 µmol/L) and trough values greater than 10 µg/mL (17.1 µmol/L).
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 amikacin levels of approximately 5.0 and 30 µg/mL (8.6 and 51.3 µmol/L).
Icterus:
Hemolysis:
Lipemia (Intralipid):
Triglycerides: No significant interference from triglycerides up to a concentration of 800 mg/dL (9.0 mmol/L).
Drugs: No interference was found at therapeutic concentrations using common drug panels.
Rheumatoid factors: No significant interference from rheumatoid factors up to a concentration of 100 IU/mL.
Total protein: No significant interference from total protein in the concentration range of 2‑12 g/dL.
In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.
For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.
ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on 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 | |
05841224 190 | ONLINE TDM Amikacin (75 tests) | System‑ID 01 6926 6 | Roche/Hitachi cobas c 701/702 |
Materials required (but not provided):
03375781 190 | Preciset TDM II calibrators | Codes 743‑748 | |
04521536 190 | TDM Control Set | Code 310 |
AMIK2: ACN 8456
Ready for use
Carefully invert reagent container several times prior to use to ensure that the reagent components are mixed.
Deselect Automatic Rerun for this application in the Utility menu, Application screen, Range tab.
Assay type | 2‑Point End | ||
Reaction time / Assay points | 10 / 23‑35 | ||
Wavelength (sub/main) | – /700 nm | ||
Reaction direction | Increase | ||
Unit | µg/mL (µmol/L) | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 167 µL | – | |
R3 | 50 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (H2O) | ||
Normal | 2.0 µL | – | – |
Decreased | 2.0 µL | – | – |
Increased | 2.0 µL | – | – |
Shelf life at 2 to 8 °C : | See expiration date on cobas c pack label |
On‑board in use and refrigerated on the analyzer: | 6 weeks |
On‑board on the Reagent Manager: | 24 hours |
Do not freeze. |
Calibrators | S1‑6: Preciset TDM II calibrators |
Calibration mode | RCM |
Calibration frequency | 6‑point calibration |
Calibration interval may be extended based on acceptable verification of calibration by the laboratory.
Traceability: This method has been standardized against USP reference standards. The calibrators are prepared to contain known quantities of amikacin in normal human serum.
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 (n = 63). The following results were obtained:
Repeatability | Mean | SD | CV |
Control 1 | 5.2 (8.9) | 0.1 (0.2) | 1.9 |
Control 2 | 15.1 (25.8) | 0.1 (0.2) | 1.0 |
Human serum A | 3.4 (5.8) | 0.1 (0.2) | 3.8 |
Human serum B | 9.2 (15.7) | 0.2 (0.3) | 2.1 |
Human serum C | 35.7 (61.0) | 0.3 (0.5) | 0.8 |
Intermediate precision | Mean | SD | CV |
Control 1 | 5.1 (8.7) | 0.2 (0.3) | 3.8 |
Control 2 | 14.4 (24.6) | 0.2 (0.3) | 1.3 |
Control 3 | 28.2 (48.2) | 0.4 (0.7) | 1.3 |
Human serum 1 | 5.0 (8.6) | 0.2 (0.3) | 3.5 |
Human serum 2 | 32.6 (55.7) | 0.4 (0.7) | 1.3 |
Results for intermediate precision were obtained on the master system cobas c 501 analyzer.
Amikacin 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 a Roche/Hitachi cobas c 501 analyzer (x).
Sample size (n) = 62 | |
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 = 1.031x + 0.161 µg/mL | y = 1.027x + 0.181 µg/mL |
τ = 0.970 | r = 0.999 |
The sample concentrations were between 1.10 and 37.6 µg/mL (1.88 and 64.3 µmol/L). |
Amikacin is a semi-synthetic aminoglycoside that exhibits bactericidal activity against a wide range of pathogens, including many organisms resistant to other aminoglycosides.
R1 | Anti‑amikacin antibody (mouse monoclonal) and human-sourced material in buffer with preservative |
R3 | Conjugated amikacin derivative microparticles, human-sourced material, and preservative |
R1 is in position B and R3 is in position C.
For in vitro diagnostic use for health care professionals. Exercise the normal precautions required for handling all laboratory reagents.
Infectious or microbial waste:
Warning: handle waste as potentially biohazardous material. Dispose of waste according to accepted laboratory instructions and procedures.
Environmental hazards:
Apply all relevant local disposal regulations to determine the safe disposal.
Safety data sheet available for professional user on request.
For USA: Caution: Federal law restricts this device to sale by or on the order of a physician.
This kit contains components classified as follows in accordance with the Regulation (EC) No. 1272/2008:
| |
Danger |
H318 | Causes serious eye damage. |
Prevention:
P280 | Wear eye protection/ face protection. |
Response:
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. Immediately call a POISON CENTER/ doctor. |
Product safety labeling follows EU GHS guidance.
Contact phone: all countries: +49-621-7590, USA: 1-800-428-2336
All human material should be considered potentially infectious. All products derived from human blood are prepared exclusively from the blood of donors tested individually and shown to be free from HBsAg and antibodies to HCV and HIV. The testing methods use assays that have been approved by the FDA or that are in compliance with the legal rules applicable to placing in vitro diagnostic medical devices for human use on the market in the European Union.
However, as no testing method can rule out the potential risk of infection with absolute certainty, the material should be handled with the same level of care as a patient specimen. In the event of exposure, the directives of the responsible health authorities should be followed.
For quality control, use control materials as listed in the “Order information” section. In addition, other suitable control material can be used.
The control intervals and limits should be adapted to each laboratory’s individual requirements. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.
Follow the applicable government regulations and local guidelines for quality control.
For specimen collection and preparation only use suitable tubes or collection containers.
Only the specimens listed below were tested and found acceptable.
Serum: Collect serum using standard sampling tubes.
Plasma: K2- or K3-EDTA or Na or Li heparin plasma.
Stability: | 8 hours capped at 15‑25 °C |
The sample types listed were tested with a selection of sample collection tubes that were commercially available at the time of testing, i.e. not all available tubes of all manufacturers were tested. Sample collection systems from various manufacturers may contain differing materials which could affect the test results in some cases. When processing samples in primary tubes (sample collection systems), follow the instructions of the tube manufacturer.
Centrifuge samples containing precipitates before performing the assay.
See the limitations and interferences section for details about possible sample interferences.
Sample stability claims were established by experimental data by the manufacturer or based on reference literature and only for the temperatures/time frames as stated in the method sheet. It is the responsibility of the individual laboratory to use all available references and/or its own studies to determine specific stability criteria for its laboratory.
Do not induce foaming of specimens. Specimens should not be repeatedly frozen and thawed.
Invert thawed specimens several times prior to testing.
Usual sampling time varies dependent upon desired measurement of peak or trough values.
In vitro test for the quantitative determination of amikacin in serum and plasma on
Kinetic interaction of microparticles in solution (KIMS) as measured by changes in light transmission.
The assay is a homogeneous immunoassay based on the principle of measuring changes in scattered light or absorbance which result when activated microparticles aggregate. The microparticles are coated with amikacin and rapidly aggregate in the presence of an amikacin antibody solution. When a sample containing amikacin is introduced, the aggregation reaction is partially inhibited, slowing the rate of the aggregation process. Antibody bound to sample drug is no longer available to promote microparticle aggregation, and subsequent particle lattice formation is inhibited. Thus, a classic inhibition curve with respect to amikacin concentration is obtained, with the maximum rate of aggregation at the lowest amikacin concentration. By monitoring the change in scattered light or absorbance, a concentration‑dependent curve is obtained.
Measuring range
0.8‑40 µg/mL (1.4‑68.4 µmol/L)
Manually dilute samples above the measuring range 1 + 1 with the Preciset TDM II Diluent (0 µg/mL) and reassay. Multiply the result by 2 to obtain the specimen value.
Lower limits of measurement
Limit of Blank, Limit of Detection and Limit of Quantitation
Limit of Blank | = 0.8 µg/mL (1.4 µmol/L) |
Limit of Detection | = 0.8 µg/mL (1.4 µmol/L) |
Limit of Quantitation | = 1.2 µg/mL (2.05 µmol/L) |
The Limit of Blank, Limit of Detection and Limit of Quantitation were determined in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP17‑A2 requirements.
The Limit of Blank is the 95th percentile value from n ≥ 60 measurements of analyte‑free samples over several independent series. The Limit of Blank corresponds to the concentration below which analyte‑free samples are found with a probability of 95 %.
The Limit of Detection is determined based on the Limit of Blank and the standard deviation of low concentration samples.
The Limit of Detection corresponds to the lowest analyte concentration which can be detected (value above the Limit of Blank with a probability of 95 %).
The Limit of Quantitation is the lowest analyte concentration that can be reproducibly measured with a total error of 20 %. It has been determined using low concentration amikacin samples.
Although optimum values may vary, peak serum values of amikacin in the range of 20 to 25 µg/mL (34.2 to 42.8 µmol/L) and trough values in the range of 5 to 10 µg/mL (8.6 to 17.1 µmol/L) are generally accepted for therapeutic effectiveness. Toxicity is associated with peak levels greater than 35 µg/mL (59.9 µmol/L) and trough values greater than 10 µg/mL (17.1 µmol/L).
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 amikacin levels of approximately 5.0 and 30 µg/mL (8.6 and 51.3 µmol/L).
Serum/plasma
Icterus:
Hemolysis:
Lipemia (Intralipid):
Triglycerides: No significant interference from triglycerides up to a concentration of 800 mg/dL (9.0 mmol/L).
Rheumatoid factors: No significant interference from rheumatoid factors up to a concentration of 100 IU/mL.
Total protein: No significant interference from total protein in the concentration range of 2‑12 g/dL.
In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.
For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.
ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on 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 further instructions, refer to the operator’s manual.
|
| Analyzer(s) on which cobas c pack(s) can be used | |
ONLINE TDM Amikacin (200 tests) | System‑ID 2015 001 | cobas c 303, cobas c 503 |
Materials required (but not provided):
03375781190 |
| Codes 20743‑20748 | |
04521536190 | TDM Control Set |
|
AMIK2X: ACN 20151
Ready for use
Carefully invert reagent container several times prior to use to ensure that the reagent components are mixed.
Test definition | |||
Reporting time | 10 min | ||
Wavelength (sub/main) | – /700 nm | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 84 µL | – | |
R3 | 25 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (H2O) | ||
Normal | 1.0 µL | – | – |
Decreased | 1.0 µL | – | – |
Increased | 1.0 µL | – | – |
For further information about the assay test definitions refer to the application parameters setting screen of the corresponding analyzer and assay.
Shelf life at 2‑8 °C: | See expiration date on cobas c pack label |
On‑board in use and refrigerated on the analyzer: | 26 weeks |
Do not freeze. |
Calibrator | S1‑6: Preciset TDM II calibrators |
Calibration mode | Non‑linear |
Calibration frequency | |
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 USP reference standards. The calibrators are prepared to contain known quantities of amikacin in normal human serum.
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).
Serum/plasma
Repeatability | Mean | SD | CV |
TDMC1a) | 5.14 | 0.152 | 2.9 |
TDMC2b) | 14.5 | 0.203 | 1.4 |
TDMC3c) | 27.4 | 0.694 | 2.5 |
Human serum 1 | 2.18 | 0.147 | 6.8 |
Human serum 2 | 10.7 | 0.159 | 1.5 |
Human serum 3 | 20.1 | 0.231 | 1.1 |
Human serum 4 | 24.2 | 0.283 | 1.2 |
Human serum 5 | 35.4 | 0.549 | 1.6 |
Intermediate precision | Mean | SD | CV |
TDMC1 FREFTDM Control Set Level I | 5.14 | 0.215 | 4.2 |
TDMC2 FREFTDM Control Set Level II | 14.4 | 0.252 | 1.7 |
TDMC3 FREFTDM Control Set Level III | 27.4 | 0.694 | 2.5 |
Human serum 1 | 1.96 | 0.223 | 11.4 |
Human serum 2 | 10.7 | 0.220 | 2.0 |
Human serum 3 | 20.2 | 0.289 | 1.4 |
Human serum 4 | 24.2 | 0.331 | 1.4 |
Human serum 5 | 35.4 | 0.589 | 1.7 |
Serum/plasma
Amikacin values for human serum and plasma samples obtained on a cobas c 503 analyzer (y) were compared with those determined using the corresponding reagent on a cobas c 501 analyzer (x).
Sample size (n) = 75 | |
Passing/Bablok LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790. | Linear regression |
y = 0.975x + 0.209 µg/mL | y = 0.991x + 0.0137 µg/mL |
τ = 0.965 | r = 0.997 |
The sample concentrations were between 1.20 and 37.5 µg/mL.
Sample size (n) = 75 | |
Passing/Bablok LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790. | Linear regression |
y = 0.967x + 0.110 µg/mL | y = 0.978x - 0.0391 µg/mL |
τ = 0.981 | r = 0.998 |
The sample concentrations were between 1.30 and 37.2 µg/mL.
Amikacin is a semi‑synthetic aminoglycoside that exhibits bactericidal activity against a wide range of pathogens, including many organisms resistant to other aminoglycosides.
R1 | Anti‑amikacin antibody (mouse monoclonal) and human‑sourced material in buffer with preservative |
R3 | Conjugated amikacin derivative microparticles, human‑sourced material, and preservative |
R1 is in position B and R3 is in position C.
For in vitro diagnostic use for health care professionals. Exercise the normal precautions required for handling all laboratory reagents.
Infectious or microbial waste:
Warning: handle waste as potentially biohazardous material. Dispose of waste according to accepted laboratory instructions and procedures.
Environmental hazards:
Apply all relevant local disposal regulations to determine the safe disposal.
Safety data sheet available for professional user on request.
For USA: Caution: Federal law restricts this device to sale by or on the order of a physician.
All human material should be considered potentially infectious. All products derived from human blood are prepared exclusively from the blood of donors tested individually and shown to be free from HBsAg and antibodies to HCV and HIV. The testing methods use assays that have been approved by the FDA or that are in compliance with the legal rules applicable to placing in vitro diagnostic medical devices for human use on the market in the European Union.
However, as no testing method can rule out the potential risk of infection with absolute certainty, the material should be handled with the same level of care as a patient specimen. In the event of exposure, the directives of the responsible health authorities should be followed.
This kit contains components classified as follows in accordance with the Regulation (EC) No. 1272/2008:
| |
Danger |
H318 | Causes serious eye damage. |
Prevention:
P280 | Wear eye protection/ face protection. |
Response:
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. Immediately call a POISON CENTER/ doctor. |
Product safety labeling follows EU GHS guidance.
Contact phone: 1-800-428-2336
For quality control, use control materials as listed in the \"Order information\" section.
In addition, other suitable control material can be used.
The control intervals and limits should be adapted to each laboratory’s individual requirements. It is recommended to perform quality control always after lot calibration and subsequently at least every 26 weeks.
Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.
Follow the applicable government regulations and local guidelines for quality control.
For specimen collection and preparation only use suitable tubes or collection containers.
Only the specimens listed below were tested and found acceptable.
Serum: Collect serum using standard sampling tubes.
Plasma: K2‑ or K3‑EDTA or Na or Li heparin plasma.
Stability: | 8 hours capped at 15‑25 °C |
48 hours capped at 2‑8 °C | |
4 weeks capped at -20 °C |
The sample types listed were tested with a selection of sample collection tubes that were commercially available at the time of testing, i.e. not all available tubes of all manufacturers were tested. Sample collection systems from various manufacturers may contain differing materials which could affect the test results in some cases. When processing samples in primary tubes (sample collection systems), follow the instructions of the tube manufacturer.
Centrifuge samples containing precipitates before performing the assay.
See the limitations and interferences section for details about possible sample interferences.
Sample stability claims were established by experimental data by the manufacturer or based on reference literature and only for the temperatures/time frames as stated in the method sheet. It is the responsibility of the individual laboratory to use all available references and/or its own studies to determine specific stability criteria for its laboratory.
Do not induce foaming of specimens. Specimens should not be repeatedly frozen and thawed.
Invert thawed specimens several times prior to testing.
Usual sampling time varies dependent upon desired measurement of peak or trough values.
In vitro test for the quantitative determination of amikacin in serum and plasma on
Kinetic interaction of microparticles in solution (KIMS) as measured by changes in light transmission.
The assay is a homogeneous immunoassay based on the principle of measuring changes in scattered light or absorbance which result when activated microparticles aggregate. The microparticles are coated with amikacin and rapidly aggregate in the presence of an amikacin antibody solution. When a sample containing amikacin is introduced, the aggregation reaction is partially inhibited, slowing the rate of the aggregation process. Antibody bound to sample drug is no longer available to promote microparticle aggregation, and subsequent particle lattice formation is inhibited. Thus, a classic inhibition curve with respect to amikacin concentration is obtained, with the maximum rate of aggregation at the lowest amikacin concentration. By monitoring the change in scattered light or absorbance, a concentration‑dependent curve is obtained.
Measuring range
0.8‑40 µg/mL (1.4‑68.4 µmol/L)
Manually dilute samples above the measuring range 1 + 1 with the Preciset TDM II Diluent (0 µg/mL) and reassay. Multiply the result by 2 to obtain the specimen value.
Lower limits of measurement
Limit of Blank, Limit of Detection and Limit of Quantitation
Limit of Blank | = 0.8 µg/mL (1.4 µmol/L) |
Limit of Detection | = 0.8 µg/mL (1.4 µmol/L) |
Limit of Quantitation | = 1.2 µg/mL (2.05 µmol/L) |
The Limit of Blank, Limit of Detection and Limit of Quantitation were determined in accordance with the CLSI (Clinical and Laboratory Standards Institute) EP17‑A2 requirements.
The Limit of Blank is the 95th percentile value from n ≥ 60 measurements of analyte‑free samples over several independent series. The Limit of Blank corresponds to the concentration below which analyte‑free samples are found with a probability of 95 %.
The Limit of Detection is determined based on the Limit of Blank and the standard deviation of low concentration samples.
The Limit of Detection corresponds to the lowest analyte concentration which can be detected (value above the Limit of Blank with a probability of 95 %).
The Limit of Quantitation is the lowest analyte concentration that can be reproducibly measured with a total error of 20 %. It has been determined using low concentration amikacin samples.
Although optimum values may vary, peak serum values of amikacin in the range of 20 to 25 µg/mL (34.2 to 42.8 µmol/L) and trough values in the range of 5 to 10 µg/mL (8.6 to 17.1 µmol/L) are generally accepted for therapeutic effectiveness. Toxicity is associated with peak levels greater than 35 µg/mL (59.9 µmol/L) and trough values greater than 10 µg/mL (17.1 µmol/L).
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 amikacin levels of approximately 5.0 and 30 µg/mL (8.6 and 51.3 µmol/L).
Serum/plasma
Icterus:
Hemolysis:
Lipemia (Intralipid):
Triglycerides: No significant interference from triglycerides up to a concentration of 800 mg/dL (9.0 mmol/L).
Rheumatoid factors: No significant interference from rheumatoid factors up to a concentration of 100 IU/mL.
Total protein: No significant interference from total protein in the concentration range of 2‑12 g/dL.
In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.
For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.
ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on 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 further instructions, refer to the operator’s manual.
Analyzer(s) on which cobas c pack(s) can be used | |||
08105383190 | ONLINE TDM Amikacin (200 tests) | System‑ID 2015 001 | cobas c 303, cobas c 503 |
Materials required (but not provided):
03375781190 |
| Codes 20743‑20748 | |
04521536190 | TDM Control Set |
|
AMIK2: ACN 20150
Ready for use
Carefully invert reagent container several times prior to use to ensure that the reagent components are mixed.
Test definition | |||
Reporting time | 10 min | ||
Wavelength (sub/main) | – /700 nm | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 84 µL | – | |
R3 | 25 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (H2O) | ||
Normal | 1.0 µL | – | – |
Decreased | 1.0 µL | – | – |
Increased | 1.0 µL | – | – |
For further information about the assay test definitions refer to the application parameters setting screen of the corresponding analyzer and assay.
Shelf life at 2‑8 °C: | See expiration date on cobas c pack label |
On‑board in use and refrigerated on the analyzer: | 26 weeks |
Do not freeze. |
S1‑6: Preciset TDM II calibrators | |
Calibrators (2‑point calibration) | S2: Preciset TDM II‑B |
Calibration mode | Non‑linear |
| 2‑point calibration Full calibration |
Calibration frequency | 2‑point calibration Full calibration |
Calibration interval may be extended based on acceptable verification of calibration by the laboratory.
Traceability: This method has been standardized against USP reference standards. The calibrators are prepared to contain known quantities of amikacin in normal human serum.
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.
Serum/plasma
Repeatability | Mean | SD | CV |
TDMC1a) | 5.14 | 0.152 | 2.9 |
TDMC2b) | 14.5 | 0.203 | 1.4 |
TDMC3c) | 27.4 | 0.694 | 2.5 |
Human serum 1 | 2.18 | 0.147 | 6.8 |
Human serum 2 | 10.7 | 0.159 | 1.5 |
Human serum 3 | 20.1 | 0.231 | 1.1 |
Human serum 4 | 24.2 | 0.283 | 1.2 |
Human serum 5 | 35.4 | 0.549 | 1.6 |
Intermediate precision | Mean | SD | CV |
TDMC1 FREFTDM Control Set Level I | 5.14 | 0.215 | 4.2 |
TDMC2 FREFTDM Control Set Level II | 14.4 | 0.252 | 1.7 |
TDMC3 FREFTDM Control Set Level III | 27.4 | 0.694 | 2.5 |
Human serum 1 | 1.96 | 0.223 | 11.4 |
Human serum 2 | 10.7 | 0.220 | 2.0 |
Human serum 3 | 20.2 | 0.289 | 1.4 |
Human serum 4 | 24.2 | 0.331 | 1.4 |
Human serum 5 | 35.4 | 0.589 | 1.7 |
The data obtained on cobas c 503 analyzer(s) are representative for cobas c 303 analyzer(s).
Serum/plasma
Amikacin values for human serum and plasma samples obtained on a cobas c 503 analyzer (y) were compared with those determined using the corresponding reagent on a cobas c 501 analyzer (x).
Sample size (n) = 75 | |
Passing/Bablok LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790. | Linear regression |
y = 0.975x + 0.209 µg/mL | y = 0.991x + 0.0137 µg/mL |
τ = 0.965 | r = 0.997 |
The sample concentrations were between 1.20 and 37.5 µg/mL.
Amikacin 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).
Sample size (n) = 75 | |
Passing/Bablok LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790. | Linear regression |
y = 0.967x + 0.110 µg/mL | y = 0.978x - 0.0391 µg/mL |
τ = 0.981 | r = 0.998 |
The sample concentrations were between 1.30 and 37.2 µg/mL.
Amikacin is a semi‑synthetic aminoglycoside that exhibits bactericidal activity against a wide range of pathogens, including many organisms resistant to other aminoglycosides.
R1 | Anti‑amikacin antibody (mouse monoclonal) and human‑sourced material in buffer with preservative |
R3 | Conjugated amikacin derivative microparticles, human‑sourced material, and preservative |
R1 is in position B and R3 is in position C.
For in vitro diagnostic use for health care professionals. Exercise the normal precautions required for handling all laboratory reagents.
Infectious or microbial waste:
Warning: handle waste as potentially biohazardous material. Dispose of waste according to accepted laboratory instructions and procedures.
Environmental hazards:
Apply all relevant local disposal regulations to determine the safe disposal.
Safety data sheet available for professional user on request.
All human material should be considered potentially infectious. All products derived from human blood are prepared exclusively from the blood of donors tested individually and shown to be free from HBsAg and antibodies to HCV and HIV. The testing methods use assays that have been approved by the FDA or that are in compliance with the legal rules applicable to placing in vitro diagnostic medical devices for human use on the market in the European Union.
However, as no testing method can rule out the potential risk of infection with absolute certainty, the material should be handled with the same level of care as a patient specimen. In the event of exposure, the directives of the responsible health authorities should be followed.
This kit contains components classified as follows in accordance with the Regulation (EC) No. 1272/2008:
Danger
H318 | Causes serious eye damage. |
Prevention:
P280 | Wear eye protection/ face protection. |
Response:
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. Immediately call a POISON CENTER/ doctor. |
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 26 weeks.
Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.
Follow the applicable government regulations and local guidelines for quality control.
For specimen collection and preparation only use suitable tubes or collection containers.
Only the specimens listed below were tested and found acceptable.
Serum: Collect serum using standard sampling tubes.
Plasma: K2‑ or K3‑EDTA or Na or Li heparin plasma.
Stability: | 8 hours capped at 15‑25 °C |
48 hours capped at 2‑8 °C | |
4 weeks capped at -20 °C |
The sample types listed were tested with a selection of sample collection tubes that were commercially available at the time of testing, i.e. not all available tubes of all manufacturers were tested. Sample collection systems from various manufacturers may contain differing materials which could affect the test results in some cases. When processing samples in primary tubes (sample collection systems), follow the instructions of the tube manufacturer.
Centrifuge samples containing precipitates before performing the assay.
See the limitations and interferences section for details about possible sample interferences.
Do
Invert thawed specimens several times prior to testing.
Usual sampling time varies dependent upon desired measurement of peak or trough values.
In vitro test for the quantitative determination of amikacin in serum and plasma on Roche/Hitachi cobas c systems.
Kinetic interaction of microparticles in solution (KIMS) as measured by changes in light transmission.
The assay is a homogeneous immunoassay based on the principle of measuring changes in scattered light or absorbance which result when activated microparticles aggregate. The microparticles are coated with amikacin and rapidly aggregate in the presence of an amikacin antibody solution. When a sample containing amikacin is introduced, the aggregation reaction is partially inhibited, slowing the rate of the aggregation process. Antibody bound to sample drug is no longer available to promote microparticle aggregation, and subsequent particle lattice formation is inhibited. Thus, a classic inhibition curve with respect to amikacin concentration is obtained, with the maximum rate of aggregation at the lowest amikacin concentration. By monitoring the change in scattered light or absorbance, a concentration‑dependent curve is obtained.
Measuring range
0.8‑40 µg/mL (1.4‑68.4 µmol/L)
Manually dilute samples above the measuring range 1 + 1 with the Preciset TDM II Diluent (0 µg/mL) and reassay. Multiply the result by 2 to obtain the specimen value.
Lower limits of measurement
Lower detection limit of the test
0.8 µg/mL (1.4 µmol/L)
The lower detection limit represents the lowest measurable analyte level that can be distinguished from zero. It is calculated as the value lying 2 standard deviations above that of the 0 µg/mL calibrator (standard 1 + 2 SD, repeatability, n = 21).
Although optimum values may vary, peak serum values of amikacin in the range of 20 to 25 µg/mL (34.2 to 42.8 µmol/L) and trough values in the range of 5 to 10 µg/mL (8.6 to 17.1 µmol/L) are generally accepted for therapeutic effectiveness. Toxicity is associated with peak levels greater than 35 µg/mL (59.9 µmol/L) and trough values greater than 10 µg/mL (17.1 µmol/L).
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 amikacin levels of approximately 5.0 and 30 µg/mL (8.6 and 51.3 µmol/L).
Serum/Plasma
Icterus:
Hemolysis:
Lipemia (Intralipid):
Rheumatoid factors: No significant interference from rheumatoid factors up to a concentration of 100 IU/mL.
Total protein: No significant interference from total protein in the concentration range of 2‑12 g/dL.
In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.
For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.
ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on 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, 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 | |
04791959 190 | ONLINE TDM Amikacin (75 tests) | System‑ID 07 6926 6 | Roche/Hitachi cobas c 311, cobas c 501/502 |
Materials required (but not provided):
03375781 190 | Preciset TDM II Calibrators | Codes 743‑748 | |
04521536 190 | TDM Control Set |
|
For cobas c 311/501 analyzers:
AMIK2: ACN 456
For cobas c 502 analyzers:
AMIK2: ACN 8456
Ready for use
Carefully invert reagent container several times prior to use to ensure that the reagent components are mixed.
Deselect Automatic Rerun for these applications in the Utility menu, Application screen, Range tab.
cobas c 311 test definition | |||
Assay type | 2‑Point End | ||
Reaction time /Assay points: | 10 / 10‑26 | ||
Wavelength (sub/main) | – /700 nm | ||
Reaction direction | Increase | ||
Unit | µg/mL | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 167 µL | – | |
R2 | 50 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 2.0 µL | – | – |
Decreased | 2.0 µL | – | – |
Increased | 2.0 µL | – | – |
cobas c 501/502 test definition | |||
Assay type | 2‑Point End | ||
Reaction time /Assay points: | 10 / 16‑38 | ||
Wavelength (sub/main) | – /700 nm | ||
Reaction direction | Increase | ||
Unit | µg/mL | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 167 µL | – | |
R2 | 50 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 2.0 µL | – | – |
Decreased | 2.0 µL | – | – |
Increased | 2.0 µL | – | – |
Shelf life at 2‑8 °C: | See expiration date on cobas c pack label |
On‑board in use and refrigerated on the analyzer : | 12 weeks |
Do not freeze. |
Calibrator | S1‑6: Preciset TDM II Calibrators |
Calibration mode | RCM |
Calibration frequency | 6‑point calibration |
Calibration interval may be extended based on acceptable verification of calibration by the laboratory.
Traceability: This method has been standardized against USP reference standards. The calibrators are prepared to contain known quantities of amikacin in normal human
Representative performance data on the analyzers are given below. Results obtained in individual laboratories may differ.
Precision was determined using human samples and controls in a modified NCCLS EP5‑A protocol (repeatability n = 63, intermediate precision n = 63). The following results were obtained on a Roche/Hitachi cobas c 501 analyzer.
Serum/Plasma
Repeatability | Mean | SD | CV | ||
µg/mL | µmol/L | µg/mL | µmol/L | % | |
Control 1 | 5.07 | 8.67 | 0.14 | 0.24 | 2.7 |
Control 2 | 14.4 | 24.6 | 0.16 | 0.27 | 1.1 |
Control 3 | 28.2 | 48.2 | 0.27 | 0.46 | 1.0 |
HS 1 | 4.98 | 8.52 | 0.13 | 0.22 | 2.6 |
HS 2 | 32.6 | 55.7 | 0.31 | 0.53 | 0.9 |
Intermediate precision | Mean | SD | CV | ||
µg/mL | µmol/L | µg/mL | µmol/L | % | |
Control 1 | 5.07 | 8.67 | 0.19 | 0.32 | 3.8 |
Control 2 | 14.4 | 24.6 | 0.19 | 0.32 | 1.3 |
Control 3 | 28.2 | 48.2 | 0.36 | 0.62 | 1.3 |
HS 1 | 4.98 | 8.52 | 0.17 | 0.29 | 3.5 |
HS 2 | 32.6 | 55.7 | 0.41 | 0.70 | 1.3 |
Serum/plasma
Amikacin values for human serum and plasma samples obtained on a Roche/Hitachi cobas c 501 analyzer (y) were compared with those determined
Roche/Hitachi 917 analyzer | Sample size (n) = 57 |
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 - 0.078 µg/mL | y = 0.986x - 0.033 µg/mL |
τ = 0.981 | r = 1.000 |
The sample concentrations were between 1.1 and 37.4 µg/mL (1.88 and 64.0 µmol/L).
COBAS INTEGRA 700 analyzer | Sample size (n) = 53 |
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 = 0.950x - 0.195 µg/mL | y = 0.949x - 0.327 µg/mL |
τ = 0.934 | r = 0.993 |
The sample concentrations were between 1.4 and 39.8 µg/mL (2.39 and 68.1 µmol/L).
Amikacin is a semi‑synthetic aminoglycoside that exhibits bactericidal activity against a wide range of pathogens, including many organisms resistant to other aminoglycosides.
R1 | Anti‑amikacin antibody (mouse monoclonal) and human‑sourced material in buffer with preservative |
R2 | Conjugated amikacin derivative microparticles, human‑sourced material, and preservative |
R1 is in position A and R2 is in position B.
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:
| |
Danger |
H318 | Causes serious eye damage. |
Prevention:
P280 | Wear eye protection/ face protection. |
Response:
P305 + P351 + P338 | IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. Immediately call a POISON CENTER/ doctor. |
Product safety labeling follows EU GHS guidance.
Contact phone: all countries: +49-621-7590, USA: 1-800-428-2336
All human material should be considered potentially infectious. All products derived from human blood are prepared exclusively from the blood of donors tested individually and shown to be free from HBsAg and antibodies to HCV and HIV. The testing methods use assays that have been approved by the FDA or that are in compliance with the legal rules applicable to placing in vitro diagnostic medical devices for human use on the market in the European Union.
However, as no testing method can rule out the potential risk of infection with absolute certainty, the material should be handled with the same level of care as a patient specimen. In the event of exposure, the directives of the responsible health authorities should be followed.
For quality control, use control materials as listed in the \"Order information\" section.
In addition, other suitable control material can be used.
The control intervals and limits should be adapted to each laboratory’s individual requirements. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.
Follow the applicable government regulations and local guidelines for quality control.
For specimen collection and preparation only use suitable tubes or collection containers.
Only the specimens listed below were tested and found acceptable.
Serum: Collect serum using standard sampling tubes.
Plasma: K2‑ or K3‑EDTA or Na or Li heparin plasma.
Stability: | 8 hours capped at 15‑25 °C |
48 hours capped at 2‑8 °C | |
4 weeks capped at -20 °C |
The sample types listed were tested with a selection of sample collection tubes that were commercially available at the time of testing, i.e. not all available tubes of all manufacturers were tested. Sample collection systems from various manufacturers may contain differing materials which could affect the test results in some cases. When processing samples in primary tubes (sample collection systems), follow the instructions of the tube manufacturer.
Centrifuge samples containing precipitates before performing the assay.
See the limitations and interferences section for details about possible sample interferences.
Sample stability claims were established by experimental data by the manufacturer or based on reference literature and only for the temperatures/time frames as stated in the method sheet. It is the responsibility of the individual laboratory to use all available references and/or its own studies to determine specific stability criteria for its laboratory.
Do not induce foaming of specimens. Specimens should not be repeatedly frozen and thawed.
Invert thawed specimens several times prior to testing.
Usual sampling time varies dependent upon desired measurement of peak or trough values.
ONLINE TDM Amikacin
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