LC-MS/MS quantification of levetiracetam, lamotrigine and 10-hydroxycarbazepine in TDM of epileptic patients.

Abstract

To minimize drug-related toxicity and monitor dosing regimens, an ultra-sensitive, simple and high-throughput analytical method for therapeutic drug monitoring is required. A novel LC-MS/MS bioassay of levetiracetam, lamotrigine and 10-hydroxycarbazepine in human plasma was established. The analytes were separated on a Hypersil GOLD™ C18 column under a 2.5 min isocratic elution after one-step protein precipitation. MS detection was performed under electrospray ionization positive-mode fitted with selected reaction monitoring. The validated ranges were 0.1-20 μg/ml for LTG, 0.3-60 μg/ml for 10-hydroxycarbazepine and levetiracetam. The intra- and inter-batches of precision and accuracy was within ±15%. The novel method met all other criteria. This method can be used to monitor drug concentrations and decision-making in epileptic patients.