Chromatography

Background: Topiramate (TPM) is a new antiepileptic drug (AED) used worldwide in patients with various types of epilepsies and also for prophylaxis of migraine. A rapid, selective, reliable, precise, accurate, and reproducible liquid chromatographic tandem mass spectrometric (LC-MS/MS) method for quantifi cation of TPM in human plasma using topiramate-d12 as an Internal Standard (IS) has been developed and validated to be used routinely for TDM of TPM.

Methods: Th e drug and IS were extracted by ether and analyzed on Symmetry® C18 column. Quantitation was achieved using ESI- interface employing MRM mode.

Results: Th e method was validated over the concentration range of 0.5–30 μg/ml (r>0.99). Intra- and inter-run precisions of TPM assay at three concentrations ranged from 0.7 to 7.8% with accuracy (bias) varied from −10.0 to 2.1% indicating good precision and accuracy. Analytical recoveries of TPM and IS from spiked human plasma were in the range of 84.1 to 90.0% and 90.0 to 111.0%, respectively. Stability of TPM in human plasma samples at diff erent conditions showed that the drug was stable under the studied conditions. Matrix eff ect study showed a lack of matrix eff ect on mass ions of TPM and IS.

Conclusions: The described method compared well when assessed by LGC TDM theme program (r>0.99). Th e suitability of the developed method for TDM was demonstrated by measuring TPM in human plasma samples of epileptic patients treated with TPM. The proposed method is appropriate for routine TDM of TPM.