Carbamazepine and Carbamazepine-10,11-epoxide measurement with the reference LC-MS/MS method and a routine immunoassay

Introduction: Carbamazepine is a common antiepileptic drug used for treatment of epilepsy and other neurologic conditions. Carbamazepine-10,11-epoxide, one of its metabolites, is pharmacologically active and its values increase with concomitant use of other anticonvulsants. This study is aimed to compare the method used in our routine laboratory with a reference LC-MS/MS method for monitoring Carbamazepine, and to compare the concentrations of the drug to one of its metabolites. Methods: plasma samples were collected from patients for whom Carbamazepine measurement had been requested. For each plasma sample, Carbamazepine was assayed on Roche Cobas with Cobas CARB4 kit (immunoassay). Carbamazepine and Carbamazepine-10,11-epoxide determination were then performed with a validated and verified LC-MS/MS technique. Results: the study population consisted of 30 subjects. No significant differences were found between the routine immunoassay and the LC-MS/MS technique using Passing-Bablok regression and Bland-Altman graph, whilst the concentrations of plasma Carbamazepine and its epoxide measured with LC-MS/MS displayed a very modest correlation (r=0.639). The ratio calculated between Carbamazepine and its epoxide displayed a broad range of values (3.37-12.55). Discussion: considering the clinical significance of Carbamazepine measurement as part of TDM, we confirmed the validity of our routinely used immunoassay as easier and faster alternative to the reference method for routine quantification of plasma Carbamazepine concentration. Considering that levels of the epoxide are unpredictable and independent from the parent drug concentrations, a more comprehensive assessment of Carbamazepine metabolites should be considered, especially when patients have uncontrolled symptoms or display challenging dose adjustment.