In vitro test for the quantitative determination of ceruloplasmin in human serum and plasma on Roche/Hitachi cobas c systems.
Immunoturbidimetric assay
Human ceruloplasmin forms a precipitate with a specific antiserum which is determined turbidimetrically.
0.03‑1.4 g/L (0.22‑10.44 µmol/L, 3‑140 mg/dL)
Determine samples having higher concentrations via the rerun function. Dilution of samples via the rerun function is a 1:3 dilution. Results from samples diluted using the rerun function are automatically multiplied by a factor of 3.
Limit of Blank | = 0.03 g/L (0.22 µmol/L, 3 mg/dL) |
Limit of Detection | = 0.03 g/L (0.22 µmol/L, 3 mg/dL) |
Limit of Quantitation | = 0.03 g/L (0.22 µmol/L, 3 mg/dL) |
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 ceruloplasmin samples.
Male: | 0.15‑0.30 g/L |
Female: | 0.16‑0.45 g/L |
Male: | 1.12‑2.24 µmol/L |
Female: | 1.19‑3.36 µmol/L |
Male: | 15‑30 mg/dL |
Female: | 16‑45 mg/dL |
*calculated by unit conversion factor
Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.
Criterion: Recovery within ± 10 % of initial value at a ceruloplasmin concentration of 0.2 g/L.
Icterus:
Hemolysis:
Lipemia (Intralipid):
Rheumatoid factors: No significant interference from rheumatoid factors up to a concentration of 100 IU/mL.
High-dose hook effect: No false result occurs up to a ceruloplasmin concentration of 5 g/L.
Drugs: No interference was found at therapeutic concentrations using common drug panels. Exception: Intralipid causes artificially high ceruloplasmin results.
In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.
For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.
ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on cobas c systems. All special wash programming necessary for avoiding carry-over is available via the cobas link. The latest version of the carry-over evasion list can be found with the
|
| Analyzer(s) on which cobas c pack(s) can be used | |
08105553190 | Ceruloplasmin (200 tests) | System‑ID 2036 001 | |
03555941190 | Calibrator f.a.s. PAC (3 × 1 mL) | Code 20589 | |
05947626160 | PreciControl ClinChem Multi 1 (4 × 5 mL) | Code 20391 | |
05947774160 | PreciControl ClinChem Multi 2 (4 × 5 mL) | Code 20392 | |
08063494190 | Diluent NaCl 9 % (123 mL) | System‑ID 2906 001 |
CER: ACN 20360
Ready for use
Reporting time | 10 min | ||
Wavelength (sub/main) | 700/340 nm | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 75 µL | – | |
R3 | 15 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 8.3 µL | 10 µL | 100 µL |
Decreased | 8.3 µL | 2.5 µL | 80 µL |
Increased | 8.3 µL | 10 µL | 100 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‑S6: C.f.a.s. PAC |
Calibration mode | Non-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 reference preparation of the IRMM (Institute for Reference Materials and Measurements) BCR470/CRM470 (RPPHS - Reference Preparation for Proteins in 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).
Repeatability | Mean | SD | CV |
PCCC1a) | 0.169 (16.9) | 0.00104 (0.104) | 0.6 |
PCCC2b) | 0.289 (28.9) | 0.00126 (0.126) | 0.4 |
Human serum 1 | 0.0866 (8.66) | 0.000962 (0.0962) | 1.1 |
Human serum 2 | 0.370 (37.0) | 0.00173 (0.173) | 0.5 |
Human serum 3 | 0.600 (60.0) | 0.00344 (0.344) | 0.6 |
Human serum 4 | 0.693 (69.3) | 0.00462 (0.462) | 0.7 |
Human serum 5 | 1.18 (118) | 0.0106 (1.06) | 0.9 |
Intermediate precision | Mean | SD | CV |
PCCC1 FREFPreciControl ClinChem Multi 1 | 0.169 (16.9) | 0.00215 (0.215) | 1.3 |
PCCC2 FREFPreciControl ClinChem Multi 2 | 0.294 (29.4) | 0.00275 (0.275) | 0.9 |
Human serum 1 | 0.0866 (8.66) | 0.00241 (0.241) | 2.8 |
Human serum 2 | 0.371 (37.1) | 0.00285 (0.285) | 0.8 |
Human serum 3 | 0.600 (60.0) | 0.00408 (0.408) | 0.7 |
Human serum 4 | 0.700 (70.0) | 0.00579 (0.579) | 0.8 |
Human serum 5 | 1.19 (119) | 0.0135 (1.35) | 1.1 |
Ceruloplasmin 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 = 0.957x + 0.0164 g/L | y = 0.970x + 0.0138 g/L |
τ = 0.967 | r = 0.999 |
The sample concentrations were between 0.033 and 1.40 g/L (3.3 and 140 mg/dL).
Ceruloplasmin values for human serum and plasma samples obtained on a cobas c 303 analyzer (y) were compared with those determined using the corresponding reagent on a cobas c 501 analyzer (x).
Passing/Bablok LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790. | Linear regression |
y = 0.963x + 0.0140 g/L | y = 1.004x + 0.00516 g/L |
τ = 0.964 | r = 0.998 |
The sample concentrations were between 0.0520 and 1.30 g/L (5.2 and 130 mg/dL).
Ceruloplasmin is an acute phase protein and transport protein. The blue‑colored glycoprotein belongs to the α2‑globulin electrophoretic fraction and contains 8 copper atoms per molecule.
Incorporation of copper into the structure occurs during the synthesis of ceruloplasmin in the hepatocytes. After secretion from the liver, ceruloplasmin migrates to copper‑requiring tissue where the copper is liberated during catabolism of the ceruloplasmin molecule. In addition to transporting copper, ceruloplasmin has a catalytic function in the oxidation of iron (Fe2+ to Fe3+), polyamines, catecholamines, and polyphenols.
Decreased concentrations occur during recessive autosomal hepatolenticular degeneration (Wilson's disease). On a pathochemical level, the disease, which is accompanied by lower ceruloplasmin synthesis, occurs as a consequence of missing Cu2+ incorporation into the molecule due to defective metallothionine. This results in pathological deposits of copper in the liver (with accompanying development of cirrhosis), brain (with neurological symptoms), cornea (Kayser‑Fleischer ring), and kidneys (hematuria, proteinuria, aminoaciduria). In homozygous carriers, ceruloplasmin levels are severely depressed. Heterozygous carriers exhibit either no decrease at all or just a mild decrease. The rare Menke's syndrome involves a genetically caused copper absorption disorder with concomitant lowering of the ceruloplasmin level. Protein loss syndromes and liver cell failures are the most important causes of acquired ceruloplasmin depressions. As ceruloplasmin is a sensitive reactant to the acute phase, increases occur during acute and chronic inflammatory processes. Great increases can lead to a green‑blue coloration of the sera. Methods for assaying ceruloplasmin include immunodiffusion, nephelometry and turbidimetry.
R1 | Accelerator |
R3 | Anti‑ceruloplasmin T antiserum (rabbit) specific for human ceruloplasmin: > 0.42 g/L; phosphate buffer; preservative |
R1 is in position B and R3 is in position C.
For in vitro diagnostic use.
Exercise the normal precautions required for handling all laboratory reagents.
Disposal of all waste material should be in accordance with local guidelines.
Safety data sheet available for professional user on request.
For USA: Caution: Federal law restricts this device to sale by or on the order of a physician.
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.
Plasma: Li‑heparin 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: LREFWHO Publication: Use of anticoagulants in diagnostic laboratory investigations, WHO/DIL/LAB/99.1 Rev.2:Jan 2002. | 8 days at 20‑25 °C |
2 weeks at 4‑8 °C | |
1 year at −20 °C |
Sample stability claims were established by experimental data by the manufacturer or based on reference literature and only for the temperatures/time frames as stated in the method sheet. It is the responsibility of the individual laboratory to use all available references and/or its own studies to determine specific stability criteria for its laboratory.
In vitro test for the quantitative determination of ceruloplasmin in human serum and plasma on Roche/Hitachi cobas c systems.
Immunoturbidimetric assay
Human ceruloplasmin forms a precipitate with a specific antiserum which is determined turbidimetrically.
0.03‑1.4 g/L (0.22‑10.44 µmol/L)
Determine samples having higher concentrations via the rerun function. Dilution of samples via the rerun function is a 1:3 dilution. Results from samples diluted using the rerun function are automatically multiplied by a factor of 3.
Limit of Blank | = 0.03 g/L (0.22 µmol/L) |
Limit of Detection | = 0.03 g/L (0.22 µmol/L) |
Limit of Quantitation | = 0.03 g/L (0.22 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 ceruloplasmin samples.
Male: | 0.15‑0.30 g/L |
Female: | 0.16‑0.45 g/L |
Male: | 1.12‑2.24 µmol/L |
Female: | 1.19‑3.36 µmol/L |
*calculated by unit conversion factor
Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.
Criterion: Recovery within ± 10 % of initial value at a ceruloplasmin concentration of 0.2 g/L.
Icterus:
Hemolysis:
Lipemia (Intralipid):
Rheumatoid factors: No significant interference from rheumatoid factors up to a concentration of 100 IU/mL.
High-dose hook effect: No false result occurs up to a ceruloplasmin concentration of 5 g/L.
Drugs: No interference was found at therapeutic concentrations using common drug panels. Exception: Intralipid causes artificially high ceruloplasmin results.
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 | |
08105553190 | Ceruloplasmin (200 tests) | System‑ID 2036 001 |
Materials required (but not provided):
03555941190 | Calibrator f.a.s. PAC (3 × 1 mL) | Code 20589 | |
05117003190 | PreciControl ClinChem Multi 1 (20 × 5 mL) | Code 20391 | |
05947626190 | PreciControl ClinChem Multi 1 (4 × 5 mL) | Code 20391 | |
05117216190 | PreciControl ClinChem Multi 2 (20 × 5 mL) | Code 20392 | |
05947774190 | PreciControl ClinChem Multi 2 (4 × 5 mL) | Code 20392 | |
08063494190 | Diluent NaCl 9 % (123 mL) | System‑ID 2906 001 |
CER: ACN 20360
Ready for use
Reporting time | 10 min | ||
Wavelength (sub/main) | 700/340 nm | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 75 µL | – | |
R3 | 15 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 8.3 µL | 10 µL | 100 µL |
Decreased | 8.3 µL | 2.5 µL | 80 µL |
Increased | 8.3 µL | 10 µL | 100 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‑S6: C.f.a.s. PAC |
Calibration mode | Non-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 reference preparation of the IRMM (Institute for Reference Materials and Measurements) BCR470/CRM470 (RPPHS - Reference Preparation for Proteins in 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).
Repeatability | Mean | SD | CV |
PCCC1a) | 0.169 | 0.00104 | 0.6 |
PCCC2b) | 0.289 | 0.00126 | 0.4 |
Human serum 1 | 0.0866 | 0.000962 | 1.1 |
Human serum 2 | 0.370 | 0.00173 | 0.5 |
Human serum 3 | 0.600 | 0.00344 | 0.6 |
Human serum 4 | 0.693 | 0.00462 | 0.7 |
Human serum 5 | 1.18 | 0.0106 | 0.9 |
Intermediate precision | Mean | SD | CV |
PCCC1 FREFPreciControl ClinChem Multi 1 | 0.169 | 0.00215 | 1.3 |
PCCC2 FREFPreciControl ClinChem Multi 2 | 0.294 | 0.00275 | 0.9 |
Human serum 1 | 0.0866 | 0.00241 | 2.8 |
Human serum 2 | 0.371 | 0.00285 | 0.8 |
Human serum 3 | 0.600 | 0.00408 | 0.7 |
Human serum 4 | 0.700 | 0.00579 | 0.8 |
Human serum 5 | 1.19 | 0.0135 | 1.1 |
Ceruloplasmin values for human serum and plasma samples obtained on
Passing/Bablok LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790. | Linear regression |
y = 0.957x + 0.0164 g/L | y = 0.970x + 0.0138 g/L |
τ = 0.967 | r = 0.999 |
The sample concentrations were between 0.033 and 1.40 g/L.
Ceruloplasmin values for human serum and plasma samples obtained on a cobas c 303 analyzer (y) were compared with those determined using the corresponding reagent on a cobas c 501 analyzer (x).
Passing/Bablok LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790. | Linear regression |
y = 0.963x + 0.0140 g/L | y = 1.004x + 0.00516 g/L |
τ = 0.964 | r = 0.998 |
The sample concentrations were between 0.0520 and 1.30 g/L.
Ceruloplasmin is an acute phase protein and transport protein. The blue‑colored glycoprotein belongs to the α2‑globulin electrophoretic fraction and contains 8 copper atoms per molecule.
Incorporation of copper into the structure occurs during the synthesis of ceruloplasmin in the hepatocytes. After secretion from the liver, ceruloplasmin migrates to copper‑requiring tissue where the copper is liberated during catabolism of the ceruloplasmin molecule. In addition to transporting copper, ceruloplasmin has a catalytic function in the oxidation of iron (Fe2+ to Fe3+), polyamines, catecholamines, and polyphenols.
Decreased concentrations occur during recessive autosomal hepatolenticular degeneration (Wilson's disease). On a pathochemical level, the disease, which is accompanied by lower ceruloplasmin synthesis, occurs as a consequence of missing Cu2+ incorporation into the molecule due to defective metallothionine. This results in pathological deposits of copper in the liver (with accompanying development of cirrhosis), brain (with neurological symptoms), cornea (Kayser‑Fleischer ring), and kidneys (hematuria, proteinuria, aminoaciduria). In homozygous carriers, ceruloplasmin levels are severely depressed. Heterozygous carriers exhibit either no decrease at all or just a mild decrease. The rare Menke's syndrome involves a genetically caused copper absorption disorder with concomitant lowering of the ceruloplasmin level. Protein loss syndromes and liver cell failures are the most important causes of acquired ceruloplasmin depressions. As ceruloplasmin is a sensitive reactant to the acute phase, increases occur during acute and chronic inflammatory processes. Great increases can lead to a green‑blue coloration of the sera. Methods for assaying ceruloplasmin include immunodiffusion, nephelometry and turbidimetry.
R1 | Accelerator |
R3 | Anti‑ceruloplasmin T antiserum (rabbit) specific for human ceruloplasmin: > 0.42 g/L; phosphate buffer; 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 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.
Plasma: Li‑heparin 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: LREFWHO Publication: Use of anticoagulants in diagnostic laboratory investigations, WHO/DIL/LAB/99.1 Rev.2:Jan 2002. | 8 days at 20‑25 °C |
2 weeks at 4‑8 °C | |
1 year at −20 °C |
Sample stability claims were established by experimental data by the manufacturer or based on reference literature and only for the temperatures/time frames as stated in the method sheet. It is the responsibility of the individual laboratory to use all available references and/or its own studies to determine specific stability criteria for its laboratory.
In vitro test for the quantitative determination of ceruloplasmin in human serum and plasma on Roche/Hitachi cobas c systems.
Immunoturbidimetric assay
Human ceruloplasmin forms a precipitate with a specific antiserum which is determined turbidimetrically.
0.03‑1.4 g/L (0.22‑10.44 µmol/L)
Determine samples having higher concentrations via the rerun function. Dilution of samples via the rerun function is a 1:3 dilution. Results from samples diluted using the rerun function are automatically multiplied by a factor of 3.
Limit of Blank | = 0.03 g/L (0.22 µmol/L) |
Limit of Detection | = 0.03 g/L (0.22 µmol/L) |
Limit of Quantitation | = 0.03 g/L (0.22 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 ceruloplasmin samples.
Male: | 0.15‑0.30 g/L |
Female: | 0.16‑0.45 g/L |
Male: | 1.12‑2.24 µmol/L |
Female: | 1.19‑3.36 µmol/L |
*calculated by unit conversion factor
Each laboratory should investigate the transferability of the expected values to its own patient population and if necessary determine its own reference ranges.
Criterion: Recovery within ± 10 % of initial value at a ceruloplasmin concentration of 0.2 g/L.
Icterus:
Hemolysis:
Lipemia (Intralipid):
Rheumatoid factors: No significant interference from rheumatoid factors up to a concentration of 100 IU/mL.
High-dose hook effect: No false result occurs up to a ceruloplasmin concentration of 5 g/L.
Drugs: No interference was found at therapeutic concentrations using common drug panels. Exception: Intralipid causes artificially high ceruloplasmin results.
In very rare cases, gammopathy, in particular type IgM (Waldenström’s macroglobulinemia), may cause unreliable results.
For diagnostic purposes, the results should always be assessed in conjunction with the patient’s medical history, clinical examination and other findings.
ACTION REQUIRED
Special Wash Programming: The use of special wash steps is mandatory when certain test combinations are run together on Roche/Hitachi cobas c systems. All special wash programming necessary for avoiding carry-over is available via the cobas link. The latest version of the carry-over evasion list can be found with the NaOHD/SMS/SCCS Method Sheet for information. For further instructions refer to the operator’s manual.
|
| Analyzer(s) on which cobas c pack(s) can be used | |
08105553 190 | Ceruloplasmin (200 tests) | System‑ID 2036 001 | Roche/Hitachi cobas c 503 |
Materials required (but not provided):
03555941 190 | Calibrator f.a.s. PAC (3 × 1 mL) | Code 20589 | |
05117003 190 | PreciControl ClinChem Multi 1 (20 × 5 mL) | Code 20391 | |
05947626 190 | PreciControl ClinChem Multi 1 (4 × 5 mL) | Code 20391 | |
05947626 160 | PreciControl ClinChem Multi 1 (4 × 5 mL, for USA) | Code 20391 | |
05117216 190 | PreciControl ClinChem Multi 2 (20 × 5 mL) | Code 20392 | |
05947774 190 | PreciControl ClinChem Multi 2 (4 × 5 mL) | Code 20392 | |
05947774 160 | PreciControl ClinChem Multi 2 (4 × 5 mL, for USA) | Code 20392 | |
08063494 190 | Diluent NaCl 9 % (123 mL) | System‑ID 2906 001 |
CER: ACN 20360
Ready for use
Reporting time | 10 min | ||
Wavelength (sub/main) | 700/340 nm | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 75 µL | – | |
R3 | 15 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 8.3 µL | 10 µL | 100 µL |
Decreased | 8.3 µL | 2.5 µL | 80 µL |
Increased | 8.3 µL | 10 µL | 100 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‑S6: C.f.a.s. PAC |
Calibration mode | Non-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 reference preparation of the IRMM (Institute for Reference Materials and Measurements) BCR470/CRM470 (RPPHS - Reference Preparation for Proteins in 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). The following results were obtained:
Repeatability | Mean | SD | CV |
PCCC1a) | 0.169 | 0.00104 | 0.6 |
PCCC2b) | 0.289 | 0.00126 | 0.4 |
Human serum 1 | 0.0866 | 0.000962 | 1.1 |
Human serum 2 | 0.370 | 0.00173 | 0.5 |
Human serum 3 | 0.600 | 0.00344 | 0.6 |
Human serum 4 | 0.693 | 0.00462 | 0.7 |
Human serum 5 | 1.18 | 0.0106 | 0.9 |
Intermediate precision | Mean | SD | CV |
PCCC1 FREFPreciControl ClinChem Multi 1 | 0.169 | 0.00215 | 1.3 |
PCCC2 FREFPreciControl ClinChem Multi 2 | 0.294 | 0.00275 | 0.9 |
Human serum 1 | 0.0866 | 0.00241 | 2.8 |
Human serum 2 | 0.371 | 0.00285 | 0.8 |
Human serum 3 | 0.600 | 0.00408 | 0.7 |
Human serum 4 | 0.700 | 0.00579 | 0.8 |
Human serum 5 | 1.19 | 0.0135 | 1.1 |
Ceruloplasmin values for human serum and plasma samples obtained on a Roche/Hitachi cobas c 503 analyzer (y) were compared with those determined using the corresponding reagent on a Roche/Hitachi cobas c 501 analyzer (x).
Passing/Bablok LREFBablok W, Passing H, Bender R, et al. A general regression procedure for method transformation. Application of linear regression procedures for method comparison studies in clinical chemistry, Part III. J Clin Chem Clin Biochem 1988 Nov;26(11):783-790. | Linear regression |
y = 0.957x + 0.0164 g/L | y = 0.970x + 0.0138 g/L |
τ = 0.967 | r = 0.999 |
The sample concentrations were between 0.033 and 1.40 g/L.
Ceruloplasmin is an acute phase protein and transport protein. The blue‑colored glycoprotein belongs to the α2‑globulin electrophoretic fraction and contains 8 copper atoms per molecule.
Incorporation of copper into the structure occurs during the synthesis of ceruloplasmin in the hepatocytes. After secretion from the liver, ceruloplasmin migrates to copper‑requiring tissue where the copper is liberated during catabolism of the ceruloplasmin molecule. In addition to transporting copper, ceruloplasmin has a catalytic function in the oxidation of iron (Fe2+ to Fe3+), polyamines, catecholamines, and polyphenols.
Decreased concentrations occur during recessive autosomal hepatolenticular degeneration (Wilson's disease). On a pathochemical level, the disease, which is accompanied by lower ceruloplasmin synthesis, occurs as a consequence of missing Cu2+ incorporation into the molecule due to defective metallothionine. This results in pathological deposits of copper in the liver (with accompanying development of cirrhosis), brain (with neurological symptoms), cornea (Kayser‑Fleischer ring), and kidneys (hematuria, proteinuria, aminoaciduria). In homozygous carriers, ceruloplasmin levels are severely depressed. Heterozygous carriers exhibit either no decrease at all or just a mild decrease. The rare Menke's syndrome involves a genetically caused copper absorption disorder with concomitant lowering of the ceruloplasmin level. Protein loss syndromes and liver cell failures are the most important causes of acquired ceruloplasmin depressions. As ceruloplasmin is a sensitive reactant to the acute phase, increases occur during acute and chronic inflammatory processes. Great increases can lead to a green‑blue coloration of the sera. Methods for assaying ceruloplasmin include immunodiffusion, nephelometry and turbidimetry.
R1 | Accelerator |
R3 | Anti‑ceruloplasmin T antiserum (rabbit) specific for human ceruloplasmin: > 0.42 g/L; phosphate buffer; 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.
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.
Plasma: Li‑heparin 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: LREFWHO Publication: Use of anticoagulants in diagnostic laboratory investigations, WHO/DIL/LAB/99.1 Rev.2:Jan 2002. | 8 days at 20‑25 °C |
2 weeks at 4‑8 °C | |
1 year at −20 °C |
Sample stability claims were established by experimental data by the manufacturer or based on reference literature and only for the temperatures/time frames as stated in the method sheet. It is the responsibility of the individual laboratory to use all available references and/or its own studies to determine specific stability criteria for its laboratory.
In vitro test for the quantitative immunological determination of ceruloplasmin in human serum and plasma on COBAS INTEGRA systems.
Immunoturbidimetric assay.
Human ceruloplasmin forms a precipitate with a specific antiserum which is determined turbidimetrically at 340 nm.
0.08‑1.4 g/L (0.597‑10.4 μmol/L or 8.00‑140 mg/dL) (typical measuring range)
The upper and lower limits of the measuring range depend on the actual calibrator value.
Determine samples having higher concentrations via the rerun function. Dilution of samples via the rerun function is a 1:3 dilution. Results from samples diluted using the rerun function are automatically multiplied by a factor of 3
Lower detection limit of the test:
0.03 g/L (0.224 μmol/L or 3.00 mg/dL)
The lower detection limit represents the lowest measurable analyte level that can be distinguished from zero. It is calculated as the value lying 3 standard deviations above that of a zero sample (zero sample + 3 SD, repeatability, n = 30).
Male: 0.15‑0.30 g/L (15.0‑30.0 mg/dL or 1.12‑2.24 μmol/L)
Female: 0.16‑0.45 g/L (16.0‑45.0 mg/dL or 1.19‑3.36 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.
Icterus:
Hemolysis:
Lipemia (Intralipid):
Drugs: No interference was found at therapeutic concentrations using common drug panels.
Rheumatoid factors: No significant interference up to a rheumatoid factors level of 400 IU/mL.
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.
Analyzer(s) on which cobas c pack(s) can be used | |||
20764663 322 | Ceruloplasmin (100 tests) | System‑ID 07 6466 3 | COBAS INTEGRA 400 plus |
Materials required (but not provided):
03555941 190 | Calibrator f.a.s. PAC (3 × 1 mL) | System‑ID 07 6810 3 | |
05117003 190 | PreciControl ClinChem Multi 1 (20 × 5 mL) | System-ID 07 7469 3 | |
05947626 190 | PreciControl ClinChem Multi 1 (4 × 5 mL) | System-ID 07 7469 3 | |
05947626 160 | PreciControl ClinChem Multi 1 (4 × 5 mL, for USA) | System-ID 07 7469 3 | |
05117216 190 | PreciControl ClinChem Multi 2 (20 × 5 mL) | System-ID 07 7470 7 | |
05947774 190 | PreciControl ClinChem Multi 2 (4 × 5 mL) | System-ID 07 7470 7 | |
05947774 160 | PreciControl ClinChem Multi 2 (4 × 5 mL, for USA) | System-ID 07 7470 7 | |
20756350 322 | NaCl Diluent 9 % (6 × 22 mL) | System‑ID 07 5635 0 |
Test CERU3, test ID 0‑666
Ready for use
Measuring mode | Absorbance |
Abs. calculation mode | Endpoint |
Reaction mode | D-R1-S-SR |
Reaction direction | Increase |
Wavelength A | 340 nm |
Calc. first/last | 33/55 |
Typical prozone effect | > 12.8 g/L (> 1280 mg/dL or > 95.5 µmol/L) |
Antigen excess check | No |
Predilution factor | 21 |
Unit | g/L |
Diluent (H2O) | ||
R1 | 100 µL | |
Sample | 20 µL | 5 µL |
SR | 20 µL | 5 µL |
150 µL |
Shelf life at 2‑8 °C | See expiration date on cobas c pack label |
8 weeks |
Calibrator | C.f.a.s. PAC |
Calibration dilution ratio | 1:6.3, 1:8.5, 1:11, 1:21, 1:40, 1:105, performed automatically by the instrument |
Calibration mode | Logit/log 5 |
Calibration replicate | Duplicate recommended |
Calibration interval | Each lot and as required following quality control procedures |
Calibration interval may be extended based on acceptable verification of calibration by the laboratory.
Enter the assigned lot‑specific ceruloplasmin value of the undiluted calibrator indicated in the package insert for C.f.a.s. PAC.
Traceability: This method has been standardized against the IFCC/BCR/CAP reference preparation CRM 470 (RPPHS 91/0619) for 14 serum proteins.
Representative performance data on the COBAS INTEGRA analyzers are given below. Results obtained in individual laboratories may differ.
Precision was determined using human samples and controls in an internal protocol with repeatability and intermediate precision (2 aliquots per run, 2 runs per day, 20 days). The following results were obtained:
Level 1 | Level 2 | |
|---|---|---|
Mean | 0.20 g/L | 0.35 g/L |
CV repeatability | 3.6 % | 2.4 % |
CV intermediate precision | 3.9 % | 2.7 % |
Ceruloplasmin values for human serum samples obtained on a COBAS INTEGRA 400 analyzer (x) with the COBAS INTEGRA Ceruloplasmin reagent were compared to those determined with the same reagent on a COBAS INTEGRA 800 analyzer (y) and with Tina‑quant Ceruloplasmin reagent on a Roche/Hitachi 917 instrument (y).
COBAS INTEGRA 800 analyzer | |
Sample size (n) = 73 | |
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 = 1.05x - 0.005 g/L | y = 1.04x - 0.001 g/L |
τ = 0.9330 | r = 0.9965 |
SD (md 95) = 0.015 | Sy.x = 0.007 |
The sample concentrations were between 0.08 and 0.68 g/L (0.597 and 5.07 μmol/L or 8.00 and 68.0 mg/dL).
Roche/Hitachi 917 analyzer | |
Sample size (n) = 82 | |
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 = 1.05x + 0.002 g/L | y = 1.03x + 0.005 g/L |
τ = 0.8886 | r = 0.9917 |
SD (md 95) = 0.023 | Sy.x = 0.010 |
The sample concentrations were between 0.08 and 0.68 g/L (0.597 and 5.07 μmol/L or 8.00 and 68.0 mg/dL).
Ceruloplasmin is a protein with a molecular weight of 150 kDa. Each molecule can reversibly bind eight atoms of copper. Ceruloplasmin carries at least 95 % of all copper in plasma. The protein is synthesized by the liver and shows an acute phase response. Decreased levels are found in primary biliary cirrhosis, primary biliary atresia, and in some cases of severe hepatitis. The decreased levels are due to the limitations of total liver metabolism rather than to a defect in specific ceruloplasmin synthesis. In some congenital disorders, such as Wilson’s disease, ceruloplasmin is also found to be decreased.
As ceruloplasmin is increasingly expressed during the acute‑phase response it is generally detected in elevated levels during all inflammatory diseases. In addition, raised levels are seen in reticuloendothelial neoplasia, biliary obstruction, estrogen therapy, and pregnancy.
Various methods have been described for the measurement of ceruloplasmin. The most commonly used are turbidimetry, nephelometry, and radial immunodiffusion.
R1 | Accelerator |
SR | Anti‑ceruloplasmin T antiserum (rabbit) specific for human ceruloplasmin > 0.42 g/L in phosphate buffer; preservative |
R1 is in position B and SR is in position C.
For in vitro diagnostic use for health care professionals. Exercise the normal precautions required for handling all laboratory reagents.
Infectious or microbial waste:
Warning: handle waste as potentially biohazardous material. Dispose of waste according to accepted laboratory instructions and procedures.
Environmental hazards:
Apply all relevant local disposal regulations to determine the safe disposal.
Safety data sheet available for professional user on request.
For USA: Caution: Federal law restricts this device to sale by or on the order of a physician.
Reference range | PreciControl ClinChem Multi 1 |
Pathological range | PreciControl ClinChem Multi 2 |
Control interval | 24 hours recommended |
Control sequence | User defined |
Control after calibration | Recommended |
For quality control, use control materials as listed in the “Order information” section. In addition, other suitable control material can be used.
The control intervals and limits should be adapted to each laboratory’s individual requirements. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.
Follow the applicable government regulations and local guidelines for quality control.
For specimen collection and preparation only use suitable tubes or collection containers.
Only the specimens listed below were tested and found acceptable.
Serum
Plasma: Li‑heparin 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.
Samples and controls are automatically prediluted 1:21 (1 + 20) with NaCl solution by the instrument.
Stability: LREFUse of Anticoagulants in Diagnostic Laboratory Investigations. WHO Publication WHO/DIL/LAB/99.1 Rev. 2: Jan 2002. | 8 days at 20‑25 °C 2 weeks at 4‑8 °C 1 year at −20 °C |
Sample stability claims were established by experimental data by the manufacturer or based on reference literature and only for the temperatures/time frames as stated in the method sheet. It is the responsibility of the individual laboratory to use all available references and/or its own studies to determine specific stability criteria for its laboratory.
In vitro test for the quantitative determination of ceruloplasmin in human serum and plasma on Roche/Hitachi cobas c systems.
Immunoturbidimetric assay.
Human ceruloplasmin forms a precipitate with a specific antiserum which is determined turbidimetrically.
Measuring range
0.03‑1.4 g/L (0.22‑10.44 µmol/L, 3‑140 mg/dL)
Determine samples having higher concentrations via the rerun function. Dilution of samples via the rerun function is a 1:3 dilution. Results from samples diluted using the rerun function are automatically multiplied by a factor of 3.
Lower limits of measurement
Lower detection limit of the test
0.03 g/L (0.22 µmol/L, 3 mg/dL)
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).
Male: | 0.15‑0.30 g/L |
Female: | 0.16‑0.45 g/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 the initial value at a ceruloplasmin concentration of 0.2 g/L (1.49 µmol/L, 20 mg/dL).
Icterus:
Hemolysis:
Lipemia (Intralipid):
Rheumatoid factors up to 100 IU/mL do not interfere.
High dose hook‑effect: No false result occurs up to a ceruloplasmin concentration of 5 g/L (37.3 μmol/L, 500 mg/dL).
Drugs: No interference was found at therapeutic concentrations using common drug panels.
Exception: Intralipid causes artificially high ceruloplasmin results.
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 not required.
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 | |
20764663 322 | Ceruloplasmin 100 tests | System‑ID 07 6466 3 | Roche/Hitachi cobas c 311, cobas c 501/502 |
03555941 190 | Calibrator f.a.s. PAC (3 x 1 mL) | Code 589 | |
04567021 190 | Prealbumin/Ceruloplasmin Control Set* | ||
Precinorm PC (3 x 1 mL) | Code 102 | ||
Precipath PC (3 x 1 mL) | Code 103 | ||
05117003 190 | PreciControl ClinChem Multi 1 (20 x 5 mL) | Code 391 | |
05947626 190 | PreciControl ClinChem Multi 1 (4 x 5 mL) | Code 391 | |
05947626 160 | PreciControl ClinChem Multi 1 (4 x 5 mL, for USA) | Code 391 | |
05117216 190 | PreciControl ClinChem Multi 2 (20 x 5 mL) | Code 392 | |
05947774 190 | PreciControl ClinChem Multi 2 (4 x 5 mL) | Code 392 | |
05947774 160 | PreciControl ClinChem Multi 2 (4 x 5 mL, for USA) | Code 392 | |
04489357 190 | Diluent NaCl 9 % (50 mL) | System‑ID 07 6869 3 |
*Not for use in the US; US customers should use a suitable commercially available control.
For cobas c 311/501 analyzers:
CER: ACN 707
For cobas c 502 analyzer:
CER: ACN 8707
Ready for use
cobas c 311 test definition | |||
Assay type | 2‑Point End | ||
Reaction time / Assay points | 10/6‑25 | ||
Wavelength (sub/main) | 700/340 nm | ||
Reaction direction | Increase | ||
Units | g/L (µmol/L, mg/dL) | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 100 µL | – | |
R2 | 20 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 11 µL | 15 µL | 150 µL |
Decreased | 11 µL | 5 µL | 160 µL |
Increased | 11 µL | 15 µL | 150 µL |
cobas c 501 test definition | |||
Assay type | 2‑Point End | ||
Reaction time / Assay points | 10/10‑36 | ||
Wavelength (sub/main) | 700/340 nm | ||
Reaction direction | Increase | ||
Units | g/L (µmol/L, mg/dL) | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 100 µL | – | |
R2 | 20 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 11 µL | 15 µL | 150 µL |
Decreased | 11 µL | 5 µL | 160 µL |
Increased | 11 µL | 15 µL | 150 µL |
cobas c 502 test definition | |||
Assay type | 2‑Point End | ||
Reaction time / Assay points | 10/10‑36 | ||
Wavelength (sub/main) | 700/340 nm | ||
Reaction direction | Increase | ||
Units | g/L (µmol/L, mg/dL) | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 100 µL | – | |
R2 | 20 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 11 µL | 15 µL | 150 µL |
Decreased | 11 µL | 5 µL | 160 µL |
Increased | 11 µL | 20 µL | 90 µL |
CERU | |
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‑S6: C.f.a.s. PAC | |
Multiply the lot | ||
S2: 0.600 | S5: 3.20 | |
S3: 1.25 | S6: 4.00 | |
S4: 2.10 | ||
Calibration mode | RCM2 | |
Calibration frequency | Full calibration |
Calibration interval may be extended based on acceptable verification of calibration by the laboratory.
Traceability: This method has been standardized against the reference preparation of the IRMM (Institute for Reference Materials and Measurements) BCR470/CRM470 (RPPHS - Reference Preparation for Proteins in 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 (3 aliquots per run, 1 run per day, 21 days). The following results were obtained:
Repeatability | Mean g/L (µmol/L, mg/dL) | SD g/L (µmol/L, mg/dL) | CV % |
Precinorm Protein | 0.283 (2.11, 28.3) | 0.004 (0.03, 0.4) | 1.6 |
Precipath Protein | 0.620 (4.62, 62.0) | 0.007 (0.05, 0.7) | 1.1 |
Human serum 1 | 0.298 (2.23, 29.8) | 0.003 (0.02, 0.25) | 0.8 |
Human serum 2 | 0.501 (3.74, 50.1) | 0.004 (0.03, 0.4) | 0.7 |
Human serum 3 | 1.30 (9.70, 130) | 0.009 (0.07, 0.9) | 0.7 |
Intermediate precision | Mean g/L (µmol/L, mg/dL) | SD g/L (µmol/L, mg/dL) | CV % |
Precinorm Protein | 0.293 (2.19, 293) | 0.004 (0.03, 0.4) | 1.4 |
Precipath Protein | 0.413 (3.08, 41.3) | 0.004 (0.03, 0.4) | 1.0 |
Human serum 3 | 0.188 (1.40, 18.8) | 0.005 (0.04, 0.5) | 2.6 |
Human serum 4 | 0.436 (3.25, 436) | 0.007 (0.05, 0.7) | 1.5 |
Ceruloplasmin values for human serum and plasma samples obtained on a Roche/Hitachi cobas c 501 analyzer (y) were compared with those determined using the corresponding reagent on a Roche/Hitachi 917 analyzer (x).
Sample size (n) = 82
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 = 0.980x + 0.012 g/L | y = 1.015x – 0.001 g/L |
τ = 0.934 | r = 0.997 |
The sample concentrations were between 0.132 and 1.32 g/L (0.984 and 9.85 µmol/L, 13.2 and 132 mg/dL). |
Ceruloplasmin is an acute phase protein and transport protein. The blue‑colored glycoprotein belongs to the α2‑globulin electrophoretic fraction and contains 8 copper atoms per molecule.
Incorporation of copper into the structure occurs during the synthesis of ceruloplasmin in the hepatocytes. After secretion from the liver, ceruloplasmin migrates to copper‑requiring tissue where the copper is liberated during catabolism of the ceruloplasmin molecule. In addition to transporting copper, ceruloplasmin has a catalytic function in the oxidation of iron (Fe2+ to Fe3+ ), polyamines, catecholamines, and polyphenols.
Decreased concentrations occur during recessive autosomal hepatolenticular degeneration (Wilson's disease). On a pathochemical level, the disease, which is accompanied by lower ceruloplasmin synthesis, occurs as a consequence of missing Cu2+ incorporation into the molecule due to defective metallothionine. This results in pathological deposits of copper in the liver (with accompanying development of cirrhosis), brain (with neurological symptoms), cornea (Kayser‑Fleischer ring), and kidneys (hematuria, proteinuria, aminoaciduria). In homozygous carriers, ceruloplasmin levels are severely depressed. Heterozygous carriers exhibit either no decrease at all or just a mild decrease. The rare Menke's syndrome involves a genetically caused copper absorption disorder with concomitant lowering of the ceruloplasmin level. Protein loss syndromes and liver cell failures are the most important causes of acquired ceruloplasmin depressions. As ceruloplasmin is a sensitive reactant to the acute phase, increases occur during acute and chronic inflammatory processes. Great increases can lead to a green‑blue coloration of the sera. Methods for assaying ceruloplasmin include immunodiffusion, nephelometry and turbidimetry.
R1 | Accelerator |
R2 | Anti‑ceruloplasmin T antiserum (rabbit) specific for human ceruloplasmin: > 0.42 g/L; phosphate buffer; preservative |
R1 is in position B and R2 is in position C.
For in vitro diagnostic use.
Exercise the normal precautions required for handling all laboratory reagents.
Disposal of all waste material should be in accordance with local guidelines.
Safety data sheet available for professional user on request.
For USA: Caution: Federal law restricts this device to sale by or on the order of a physician.
For quality control, use control materials as listed in the \"Order information\" section.
In addition, other suitable control material can be used.
The control intervals and limits should be adapted to each laboratory’s individual requirements. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.
Follow the applicable government regulations and local guidelines for quality control.
For specimen collection and preparation only use suitable tubes or collection containers.
Only the specimens listed below were tested and found acceptable.
Serum.
Plasma: Li‑heparin 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.
LREFWHO Publication: Use of anticoagulants in diagnostic laboratory investigations, WHO/DIL/LAB/99.1 Rev.2:Jan 2002. | 8 days at 20‑25 °C |
2 weeks at 4‑8 °C | |
1 year at -20 °C |
In vitro test for the quantitative determination of ceruloplasmin in human serum and plasma on Roche/Hitachi cobas c systems.
Immunoturbidimetric assay.
Human ceruloplasmin forms a precipitate with a specific antiserum which is determined turbidimetrically.
Measuring range
0.03‑1.4 g/L (0.22‑10.44 µmol/L, 3‑140 mg/dL)
Determine samples having higher concentrations via the rerun function. Dilution of samples via the rerun function is a 1:3 dilution. Results from samples diluted using the rerun function are automatically multiplied by a factor of 3.
Lower limits of measurement
Lower detection limit of the test
0.03 g/L (0.22 µmol/L, 3 mg/dL)
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 (< 0.03 g/L) will not be flagged by the instrument.
Male: | 0.15‑0.30 g/L |
Female: | 0.16‑0.45 g/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 the initial value at a ceruloplasmin concentration of 0.3 g/L (2.24 µmol/L, 30 mg/dL).
Icterus:
Hemolysis:
Lipemia (Intralipid):
Rheumatoid factors up to 100 IU/mL do not interfere.
High dose hook‑effect: No false result occurs up to a ceruloplasmin concentration of 5 g/L (37.3 µmol/L, 500 mg/dL).
Drugs: No interference was found at therapeutic concentrations using common drug panels.
Exception: Intralipid causes artificially high ceruloplasmin results.
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 not required. The latest version of the carry‑over evasion list can also 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 | |
05950848 190 | Ceruloplasmin (150 tests) | System‑ID 03 6466 3 | Roche/Hitachi cobas c 701/702 |
Materials required (but not provided):
03555941 190 | Calibrator f.a.s. PAC (3 x 1 mL) | Code 589 | |
04567021 190 | Prealbumin/Ceruloplasmin Control Set* | ||
Precinorm PC (3 x 1 mL) | Code 102 | ||
Precipath PC (3 x 1 mL) | Code 103 | ||
05117003 190 | PreciControl ClinChem Multi 1 (20 x 5 mL) | Code 391 | |
05947626 190 | PreciControl ClinChem Multi 1 (4 x 5 mL) | Code 391 | |
05947626 160 | PreciControl ClinChem Multi 1 (4 x 5 mL, for USA) | Code 391 | |
05117216 190 | PreciControl ClinChem Multi 2 (20 x 5 mL) | Code 392 | |
05947774 190 | PreciControl ClinChem Multi 2 (4 x 5 mL) | Code 392 | |
05947774 160 | PreciControl ClinChem Multi 2 (4 x 5 mL, for USA) | Code 392 | |
05172152 190 | Diluent NaCl 9 % (119 mL) | System‑ID 08 6869 3 |
*Not for use in the US; US customers should use a suitable commercially available control.
CER: ACN 8707
Ready for use
cobas c 701/702 test definition | |||
Assay type | 2‑Point End | ||
Reaction time / Assay points | 10/19‑33 | ||
Wavelength (sub/main) | 700/340 nm | ||
Reaction direction | Increase | ||
Units | g/L (µmol/L, mg/dL) | ||
Reagent pipetting | Diluent (H2O) | ||
R1 | 100 µL | – | |
R3 | 20 µL | – | |
Sample volumes | Sample | Sample dilution | |
Sample | Diluent (NaCl) | ||
Normal | 11 µL | 15 µL | 150 µL |
Decreased | 11 µL | 5 µL | 160 µL |
Increased | 11 µL | 20 µL | 90 µL |
CERU | |
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-S6: C.f.a.s. PAC | |
Multiply the lot‑specific C.f.a.s. PAC calibrator value by the factors below to determine the standard concentrations for the 6‑point calibration curve: | ||
S2: 0.600 | S5: 3.20 | |
S3: 1.25 | S6: 4.00 | |
S4: 2.10 | ||
Calibration mode | RCM2 | |
Calibration frequency | Full calibration |
Calibration interval may be extended based on acceptable verification of calibration by the laboratory.
Traceability: This method has been standardized against the reference preparation of the IRMM (Institute for Reference Materials and Measurements) BCR470/CRM470 (RPPHS - Reference Preparation for Proteins in 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 (3 aliquots per run, 1 run per day, 21 days). The following results were obtained:
Repeatability | Mean g/L (µmol/L, mg/dL) | SD g/L (µmol/L, mg/dL) | CV % |
Precinorm PC | 0.299 (2.23, 29.9) | 0.004 (0.03, 0.4) | 1.4 |
Precipath PC | 0.644 (4.80, 64.4) | 0.006 (0.04, 0.6) | 1.0 |
Human serum A | 0.290 (2.16, 29.0) | 0.005 (0.04, 0.5) | 1.6 |
Human serum B | 0.458 (3.42, 45.8) | 0.004 (0.03, 0.4) | 0.9 |
Human serum C | 1.26 (9.40, 126) | 0.01 (0.07, 1) | 0.9 |
Intermediate precision | Mean g/L (µmol/L, mg/dL) | SD g/L (µmol/L, mg/dL) | CV % |
Precinorm Protein | 0.293 (2.19, 29.3) | 0.004 (0.03, 0.4) | 1.4 |
Precipath Protein | 0.413 (3.08, 41.3) | 0.004 (0.03, 0.4) | 1.0 |
Human serum 1 | 0.188 (1.40, 18.8) | 0.005 (0.04, 0.5) | 2.6 |
Human serum 2 | 0.436 (3.25, 43.6) | 0.007 (0.05, 0.7) | 1.5 |
Results for intermediate precision were obtained on the master system cobas c 501 analyzer.
Ceruloplasmin 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) = 67
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 = 0.990x - 0.008 g/L | y = 0.943x + 0.017 g/L |
τ = 0.897 | r = 0.989 |
The sample concentrations were between 0.212 and 1.15 g/L (1.58 and 8.58 µmol/L, 21.2 and 115 mg/dL). |
Ceruloplasmin is an acute phase protein and transport protein. The blue‑colored glycoprotein belongs to the α2‑globulin electrophoretic fraction and contains 8 copper atoms per molecule.
Incorporation of copper into the structure occurs during the synthesis of ceruloplasmin in the hepatocytes. After secretion from the liver, ceruloplasmin migrates to copper-requiring tissue where the copper is liberated during catabolism of the ceruloplasmin molecule. In addition to transporting copper, ceruloplasmin has a catalytic function in the oxidation of iron (Fe2+ to Fe3+), polyamines, catecholamines, and polyphenols.
Decreased concentrations occur during recessive autosomal hepatolenticular degeneration (Wilson's disease). On a pathochemical level, the disease, which is accompanied by lower ceruloplasmin synthesis, occurs as a consequence of missing Cu2+ incorporation into the molecule due to defective metallothionine. This results in pathological deposits of copper in the liver (with accompanying development of cirrhosis), brain (with neurological symptoms), cornea (Kayser‑Fleischer ring), and kidneys (hematuria, proteinuria, aminoaciduria). In homozygous carriers, ceruloplasmin levels are severely depressed. Heterozygous carriers exhibit either no decrease at all or just a mild decrease. The rare Menke's syndrome involves a genetically caused copper absorption disorder with concomitant lowering of the ceruloplasmin level. Protein loss syndromes and liver cell failures are the most important causes of acquired ceruloplasmin depressions. As ceruloplasmin is a sensitive reactant to the acute phase, increases occur during acute and chronic inflammatory processes. Great increases can lead to a green-blue coloration of the sera. Methods for assaying ceruloplasmin include immunodiffusion, nephelometry and turbidimetry.
R1 | Accelerator |
R3 | Anti‑ceruloplasmin T antiserum (rabbit) specific for human ceruloplasmin: > 0.42 g/L; phosphate buffer; 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.
For quality control, use control materials as listed in the \"Order information\" section.
In addition, other suitable control material can be used.
The control intervals and limits should be adapted to each laboratory’s individual requirements. Values obtained should fall within the defined limits. Each laboratory should establish corrective measures to be taken if values fall outside the defined limits.
Follow the applicable government regulations and local guidelines for quality control.
For specimen collection and preparation only use suitable tubes or collection containers.
Only the specimens listed below were tested and found acceptable.
Serum.
Plasma: Li‑heparin 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.
LREFWHO Publication: Use of anticoagulants in diagnostic laboratory investigations, WHO/DIL/LAB/99.1 Rev.2:Jan 2002. | 8 days at 20‑25 °C |
2 weeks at 4‑8 °C | |
1 year at -20 °C |
Ceruloplasmin
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