Estimation of Carbamazepine and Carbamazepine-10,11-Epoxide Concentrations in Plasma Using Mathematical Equations Generated With Two Carbamazepine Immunoassays

Abstract

Carbamazepine is metabolized to an active metabolite known as carbamazepine-10,11-epoxide, or simply the "epoxide" metabolite. The presence of this metabolite can have clinically significant implications in therapeutic drug monitoring of carbamazepine, but accurate quantification of the epoxide metabolite is currently limited to chromatographic techniques. In this study, mathematical equations are proposed for the estimation of carbamazepine and epoxide metabolite concentrations based on values generated by common carbamazepine immunoassays. Three immunoassays were studied: particle-enhanced turbidimetric inhibition immunoassay (PETINIA, Siemens Healthcare Diagnostics, Deerfield, IL), ADVIA Centaur (Siemens Healthcare Diagnostics), and a cloned enzyme donor immunoassay (CEDIA; Roche, Indianapolis, IN). Equations were based on observed cross-reactivity of epoxide with the PETINIA (average, 96.2%; range, 86.6%-105.7%) and epoxide cross-reactivity with the ADVIA Centaur assay (average, 6.5%; range, 5.3%-7.7%). In addition, equations were developed using average cross-reactivity of epoxide with the PETINIA and with the CEDIA. Values determined by calculation correlated well with carbamazepine and epoxide concentrations in supplemented and patient samples, for which values of carbamazepine (2.2-12.0 microg/mL [9-51 micromol/L]) and the epoxide metabolite (0.6-2.4 microg/mL) were also verified by liquid chromatography-tandem mass spectrometry.

Detection of 22 antiepileptic drugs by ultra‐performance liquid chromatography coupled with tandem mass spectrometry applicable to routine therapeutic drug monitoring

“…These results were consistent with the report that antibodies for these two drugs showed cross‐reactivity with their metabolites (Neels et al ., ). Since the PETINIA method was reported to show a high level of cross‐reactivity for carbamazepine‐10,11‐epoxide (McMillin et al ., ), we compared the sum of carbamazepine and its epoxide concentrations determined by the UPLC‐MS/MS method with carbamazepine concentrations determined by this immunoassay. However, the sum was still smaller than the immunoassay values; this indicates that the antibody for carbamazepine may have cross‐reacted not only with carbamazepine‐10,11‐epoxide but also with its other metabolites.…”

Therapeutic drug monitoring and methods of quantitation for carbamazepine

“…In one case immunoassays were used to generate mathematical equations for determination of carbamazepine and its metabolite in plasma (19). Tables 2 to 5 Results for accuracy are presented as minimum and maximum values obtained for inter-day and intra-day, where applicable.…”

Interference in Immunoassays Used for Monitoring Anticonvulsants and the Usefulness of Monitoring Free Anticonvulsants

“…The authors observed a good correlation between epoxide concentrations obtained by using mathematical equations with true epode concentrations determined by LC/MS/MS(24) . After calculating the value of y , value of x can be easily determined.…”