engleski

Comparison Of İmmunochemistry Method For Determination Of Carbamazepine Concentration With Liquid Chromatography Tandem Mass Spectrometry Method

Background-Aim: Carbamazepine is an anticonvulsant used in the treatment of epilepsy. It metabolizes into the carbamazepine-10, 11-epoxide that has pharmacological effect similar to carbamazepine. Comedication and several pathophysiological conditions affect metabolism of carbamazepine. Routine monitoring of carbamazepine concentrations is recommended and is carried out by immunoassays and by chromatographic methods. These techniques differ in many aspects. The aims of this study were: I) to assess the effect of comedication on percentage of epoxide metabolite ; II) to compare the chemiluminescent microparticle immunoassay (CMIA) for determination of carbamazepine concentrations with the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Materials and Methods: This study comprised of 54 patients with a median age 30 years (range 10-74) referred to the Institute of Clinical Laboratory Diagnostics, Osijek University Hospital for carbamazepine monitoring. Venous blood samples were taken in fasting state, before taking the next dose of the drug, using a 6 ml tube containing a clot activator (Becton-Dickinson, Franklin Laes, NJ, USA, Ref 368815). Serum samples were analyzed using the CMIA on the Arhitect i1000SR (Abbott Laboratories, Lake Forest, USA) analyzer and by chromatographic technique using LCMS/MS-8040 (Shimadzu, Kyoto, Japan) analyzer. Informations about patient’s comedication were collected. Statistical analysis was performed using MedCalc for Windows, version 12.4.0.0. (MedCalc Software, Marikerke, Belgium). The t-test test was performed for group comparisons (35 patient with comedication vs 19 patients who received only carbamazepine). Passing-Bablok regression analysis and Bland-Altman analysis were performed for methods comparison. P = 0.05 was considered statistically significant. Results: The average level of carbamazepine-10, 11- epoxide in patients with comedication was 14 %, while in patients who received only carbamazepine was 12%. Statistically significant difference in epoxide percentages between those groups was obtained using t-test (P = 0.020 ; 95%CI -5.14 to -0.46). Passing-Bablok regression analysis showed proportional differences between the measured values obtained by two methods [y = − 0.52(95%CI-2.59–1.57) + 0.89(95%CI 0.82– 0.98)x]. The results of the Cusum test show no significant deviation from linearity (P = 0.92). Bland and Altman analysis showed that all measurement results, except one, were within the ±1.96 SD range. The mean difference between the two measurements was 3.5 ± 1.41 μmol/L. Results of carbamazepine concentrations measured by LCMS/MS were higher than those obtained with the CMIA method. Conclusion: Comparison study showed that CMIA on Arhitect i1000SR and LCMS/MS method cannot be used interchangeably. Comedication influences the epoxide percentage, so it’s monitoring along the carbamazepine is useful in such patients. LCMS/MS is preferred method in such cases since it fulfills the requirements for epoxide measurement. However, the simplicity of analysis performing and the ability of performing random access testing using CMIA on Arhitect i1000SR are advantages over LCMS/MS method which makes it suitable for urgent diagnostics.

carbamazepine, carbamazepine-10, 11-epoxide, immunoassay, LCMS/MS

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