Determination of carbamazepine and its metabolite carbamazepine-10,11-epoxide in serum with gas-chromatography mass spectrometry.
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% and 5.7%. The detection limit was 10 micrograms/l and the recovery 82.5% for carbamazepine epoxide and 92.5% for carbamazepine. A fast and simple gas chromatographic method for the routine therapeutic monitoring of carbamazepine and carbamazepine epoxide was developed. The simultaneous determination of the serum levels of carbamazepine epoxide and carbamazepine offers the possibility of measuring the total drug concentration, as well as that of its metabolite, while considering the results of clinical response and the special features of carbamazepine's enzymatic biotransformation through epoxidation with the formation of its metabolite.
Minkova
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Department of Pharmacology and Drug Toxicology, Medical University-Plovdiv, Sofia, Bulgaria.
Getova
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D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000097:blood*; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D007223:Infant; D008875:Middle Aged
D000927:Anticonvulsants; D002220:Carbamazepine; C012227:carbamazepine epoxide