A comparison of two FDA approved lamotrigine immunoassays with ultra-high performance liquid chromatography tandem mass spectrometry

Background: Lamotrigine is an anti-epileptic drug used as adjunct therapy for seizures. Lamotrigine is commonly used in pregnant women with epilepsy, a population in which therapeutic drug monitoring (TDM) is useful to optimize dose. Drug-drug interactions that can induce or inhibit metabolism or elimination and impaired hepatic function are also possible indications for lamotrigine TDM. Chromatographic techniques are currently used for performing most TDM of lamotrigine, but this may change, as automated immunoassays were recently introduced. Methods: Immunoassays available through Seradyn and ARK Diagnostics were validated using a Beckman AU400e automated chemistry analyzer. The intra-day precision was accessed with 5 replicates of three quality control materials, and inter-assay precision was estimated by assaying the same material over 4 days. Linearity was evaluated by serially diluting a spiked sample and measuring it in duplicate. The 2 methods were compared with ultra high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) using 44 authentic patient specimens. Results: The intra-day (n = 5) and inter-assay (n = 20) coefficients of variation were <= 7.5% for the 3 levels tested. The analytical measurement ranges were confirmed as stated by the manufacturers (0 or 1-40 mu g/ml). The percent recovery of the quality control materials and Deming regression for the 44 patient results showed good agreement of both immunoassays when compared to the UPLC-MS/MS assay. Conclusion: The lamotrigine assays studied here produced a slightly lower result than UPLC-MS/MS but were precise and easy to perform. (C) 2011 Elsevier B.V. All rights reserved.