Drug interference in clinical chemistry: recommendation of drugs and their concentrations to be used in drug interference studies.

A group of international experts prepared two lists of drugs with their serum/plasma and urine concentrations, which should be used when evaluating the performance of a new laboratory method. The two lists were verified by running in vitro interference studies in three European laboratories on Hitachi instruments. The study identified the following new interferants: acid phosphatase in serum by ibuprofen and theophylline; non-prostatic acid phosphatase in serum by cefoxitin and doxycycline; creatine kinase MB in serum by doxycycline; total bilirubin in serum (Jendrassik-Grof method) by rifampicin and intralipid; total bilirubin in serum (DPD method) by intralipid; creatinine in serum (Jaffe method) by cefoxitin; fructosamine in serum by levodopa and methyldopa; uric acid in serum by levodopa, methyldopa and tetracycline; carbamazepine in serum by doxycycline, levodopa, methyldopa and metronidazole; digitoxin in serum by rifampicin; phenytoin in serum by doxycycline, ibuprofen, metronidazole and theophylline; theophylline in serum by acetaminophen, cefoxitin, doxycycline, levodopa, phenylbutazone and rifampicin; tobramycin in serum by cefoxitin, doxycycline, levodopa, rifampicin and phenylbutazone; valproic acid in serum by phenylbutazone; C3 in serum by intralipid; C4 in serum by doxycycline; rheumatoid factor in serum by ibuprofen and metronidazole; pancreatic amylase and total amylase in urine by acetylcysteine, ascorbic acid, cefoxitin, gentamicin, levodopa, methyldopa and ofloxacin; magnesium in urine by acetylcysteine, gentamicin and methyldopa; beta2-microglobulin in urine by ascorbic acid; total protein in urine by ascorbic acid, Ca-dobesilate and phenylbutazone. Interference in acid phosphatase, creatine kinase MB and bilirubin methods was observed at very low analyte concentrations, and therefore it may not be evident at higher concentrations. The study confirmed the usefulness of the recommendation.

Analyses with the KODAK-Ektachem. Accuracy control using reference method values and the influence of protein concentration. Part I. Electrolytes.

The reliability of electrolyte determinations with the Ektachem 700 was evaluated by various means including the use of reference method values. The influence of protein concentration, which may alter the viscosity and hence the speed of diffusion, was systematically investigated by using samples of varying protein concentration obtained by ultracentrifugation. Calcium. The mean bias between Ektachem results and reference method values of 9 control sera was -7.3%. In a comparative study with native sera a negative bias was not obtained. The accuracy was independent of the protein concentration. Chloride. The mean bias was -0.1% compared with reference method values. As might be expected, the difference between chloride values with Ektachem--using a "direct" ion-selective electrode--and determinations by coulometry increased with increasing protein concentrations. Magnesium. A negative bias (-5.0%) was obtained in accuracy control with reference method values, and to a smaller extent in a comparative study with native sera. An influence of the protein concentration on the magnesium determination was not observed. Phosphate. Accuracy control by method-dependent assigned values and a comparative study with native sera showed a positive bias. Ektachem results depend on the protein concentration. At 120 g/l protein the bias was +13.6%. Potassium. The mean bias, with respect to reference method values, was -1.2%. At high concentrations of proteins of "normal" composition, Ektachem results agree with measurements by flame atomic emission spectrometry; in paraproteinaemic sera the values are higher. Sodium. The mean inaccuracy was 3.3%, compared with reference method values. The dependence on the amount and composition of the total protein was similar to that found for potassium analysis.

Analyses with the KODAK-Ektachem. Accuracy control using reference method values and the influence of protein concentration. Part II. Substrates.

The reliability of the determination of the most common substrates with the Ektachem 700 was evaluated. Accuracy control was performed in various ways including the comparison of results with reference method values. The influence of protein concentration was investigated systematically using sera containing varying amounts of protein obtained by ultracentrifugation. Bilirubin. Deviation from the reference method values was within limits of the guidelines (Dt. Arztebl. 85 (1988) B517-B532). The influence of protein concentration was negligible. Cholesterol. The results agreed well with the reference method values. The method was not influenced by different protein concentrations. Creatinine. The results were in good agreement with reference method values, when the method was calibrated with the primary assigned values of the calibrators. At high protein concentrations, the results were higher than those of the comparative method. Glucose. The mean deviation from the reference method values was 1.0%. There was a clear positive bias at high protein concentrations. Protein. The results from the Ektachem deviated from the reference method values by -6.8%. Total glycerol (triacylglycerols). In the analysis of control sera, the Ektachem values differed greatly (+32.1%) from the reference method values. This difference was not found in a comparative study with native sera. At high protein concentrations the Ektachem results were higher than those of the comparative method. Urea. The results were lower than the method-dependent assigned values (-16.6%). This deviation was not observed in a comparative study with native sera. Interference by protein was not observed. Uric acid. In accuracy control with reference method values, a small bias was observed (+3.3%), which increased at high protein concentrations.

Haemolysis as an interference factor in clinical chemistry.

Using fully mechanized analytical equipment, interference by haemolysis in the determination of 26 clinical chemical parameters was determined quantitatively by adding haemolysate to serum. Haemoglobin concentrations up to 6.6 g/l caused essentially no interference in the following determinations: albumin (immuno-nephelometric), alpha-amylase, calcium, chloride, cholesterol, cholinesterase, creatinine, iron, glucose, glutamate dehydrogenase, uric acid, urea, sodium, inorganic phosphate, total protein, transferrin and triglycerides. In the presence of haemoglobin, erroneously high values were found for: lactate dehydrogenase (haemoglobin higher than 0.2 g/l), aspartate aminotransferase, potassium and acid phosphate (haemoglobin higher than 1.5 g/l), creatine kinase (haemoglobin higher than 2.5 g/l) and alanine aminotransferase (haemoglobin higher than 3.4 g/l). Erroneously low values were found for bilirubin (haemoglobin higher than 0.8 g/l), alkaline phosphatase and albumin (by electrophoresis) (haemoglobin higher than 1.5 g/l) and gamma-glutamyltransferase (haemoglobin higher than 3.0 g/l).

A multicentre european evaluation of the Kodak EKTACHEM GLU/BUN analyzer using NCCLS guidelines and other approaches.

This paper describes the field performance of the Kodak EKTACHEM GLU/BUN Analyzer for glucose and urea. NCCLS protocols PSEP-2, 3 an 4 were used which enable manufacturers to establish performance claims concerning the precision and accuracy of an analytical system. This multicentre trial used four analysers in four European countries, United Kingdom, France, West Germany and Italy to assess within and between laboratory performances. Freeze dried control materials were used for the performance check experiment PSEP-2 and for the replication experiment PSEP-3. The replication study, although very time consuming, was straight forward to undertake and the results were comparable between centres. Compliance with the protocol for comparison of methods experiment PSEP-4 in which laboratories used their own hospital patient samples was more difficult. The problems with obtaining suitable samples and the performance of comparative methods are discussed in detail.

Comparison of 9 methods for the determination of cholesterol.

Seven enzymatic procedures for the determination of cholesterol in serum were compared with the Liebermann-Burchard- and a gas-chromatographic method. Using a decision matrix all methods could be ranked according to reliability and practicability . With the exception of the cholesterol oxidase-coupled Kageyama principle and the Liebermann-Burchard procedure, all the other methods showed similar reliability.