Determination of carbamazepine and its metabolite carbamazepine-10,11-epoxide in serum with gas-chromatography mass spectrometry

作者：Galya D Minkova, Damianka P. Getova · 发表于：Methods and Findings in Experimental and Clinical Pharmacology · 年份：2001 · DOI：10.1358/mf.2001.23.9.662144 · 被引用次数：21 · 研究领域：Epilepsy research and treatment、Pharmacological Effects and Toxicity Studies、Forensic Toxicology and Drug Analysis

Carbamazepine, one of the most often used antiepileptic drugs, undergoes enzyme biotransformation through epoxidation with the formation of its metabolite, carbamazepine-10,11-epoxide (carbamazepine epoxide). The determination of carbamazepine epoxide is clinically significant in therapeutic drug monitoring as it decreases the risk of toxic reactions and increases the possibility of reaching the expected therapeutic result. The aim of this study was to introduce a gas chromatographic method with mass spectrometric detection to simultaneously determine the serum levels of carbamazepine and carbamazepine epoxide. Blood samples from 80 epileptic patients aged between 1 and 63 years were analyzed. All patients were taking carbamazepine as monotherapy and had achieved the steady state serum drug concentration. A microcolumn extraction of carbamazepine and carbamazepine epoxide was obtained by elution. A gas chromatograph with a mass spectrometer and a 25 m x 0.2 mm ID, 0.33 micron film thickness, crosslinked 5% phenyl-methylsilicone capillary column HP-5 was used. The coefficients of correlation for the calibration plots obtained for carbamazepine epoxide and carbamazepine were 0.988 and 0.995, respectively. The precision, tested for n = 20, showed coefficients of variation within one day as follows: carbamazepine epoxide: 11.0% and 6.55%; carbamazepine: 11.8% and 5.4%. The coefficients of variation from day to day were: carbamazepine epoxide: 9.4% and 6.83%; carbamazepine: 8.5% a...