title: 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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, TX 77030, USA.
authors.forename: Gwendolyn A
authors.initials: GA
authors.lastname: McMillin
authors.forename: Joetta M
authors.initials: JM
authors.lastname: Juenke
authors.forename: Gertie
authors.initials: G
authors.lastname: Tso
authors.forename: Amitava
authors.initials: A
authors.lastname: Dasgupta
mesh_terms: D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood / Q000276:immunology; D002851:Chromatography, High Pressure Liquid; D019295:Computational Biology; D003429:Cross Reactions / Q000276:immunology; D017248:Enzyme Multiplied Immunoassay Technique / Q000706:statistics & numerical data; D016231:Fluorescence Polarization Immunoassay / Q000706:statistics & numerical data; D006801:Humans; D007118:Immunoassay / Q000706:statistics & numerical data*; D009391:Nephelometry and Turbidimetry / Q000706:statistics & numerical data; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D002220:Carbamazepine; C012227:carbamazepine epoxide