Abstracts

Rationale: Epilepsy is a medical condition that produces seizures affecting a variety of mental and physical functions. Oxcarbazepine (OXC) and eslicarbazepine acetate are second and third generation antiepileptic drugs (AED) respectively. These prodrugs are metabolized to 10-monohydroxy derivative (MHD), the active agent. Serum levels of MHD usually range 3 µg/mL to 35 µg/mL. Here an ARK enzyme immunoassay for therapeutic drug monitoring (TDM) of MHD is described. Both the S and R enantiomers of the active metabolite are detected.Methods: The ARK™ Oxcarbazepine Metabolite Assay is a liquid stable homogeneous enzyme immunoassay, consisting of two reagents, 6 calibrators (0.0, 2.0, 5.0, 12.0, 25.0 and 50.0 µg/mL) and 3 controls (3.0, 10.0 and 30.0 µg/mL). The performance of the ARK assay was evaluated on the Beckman Coulter AU480® analyzer. Precision, limit of quantitation (LOQ), recovery, specificity and method comparison were studied.Results: Total precision ranged 5.5% to 6.5%CV and within-run precision ranged 3.8% to 4.8%CV in a 20-day study using quality controls and spiked serum samples. Acceptable quantitation and recovery was observed from 1.0 µg/mL (LOQ) to 35.0 µg/mL. The assay crossreacted with structurally similar oxcarbazepine (22.2%), eslicarbazepine acetate (22.1%), and carbamazepine (20.4%) and its metabolites (cis-10, 11-dihydroxy carbamazepine, dihydro-carbamazepine, and carbamazepine epoxide). The assay did not crossreact with other AEDs tested (gabapentin, lamotrigine, levetiracetam, topiramate, and zonisamide). The assay was not interfered by endogenous substances or other potentially coadministered drugs tested. One hundred specimens (1.7 to 34.3 µg/mL) were assayed and gave the following Passing Bablock regression results when compared to LC/MS/MS values: ARK = 1.01 LC/MS/MS - 0.38 (r2=0.96).Conclusions: The ARK™ Oxcarbazepine Metabolite Assay measures oxcarbazepine MHD in human serum with excellent precision, recovery and clinical accuracy versus LC/MS/MS. Care should be taken regarding interpretation when coadministration of carbamazepine occurs. Ability to measure trough levels of oxcarbazepine MHD with high accuracy and fast turn-around time makes this method clinically useful for TDM.