Therapeutic drug monitoring of topiramate by liquid chromatography-tandem mass spectrometry

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 tandem mass spectrometric (MS/MS) method for quantification of TPM in human plasma using topiramate-d(12) as an internal standard (IS) has been developed and validated to be used routinely for TDM of TPM. Methods: The drug and IS were extracted by ether and analyzed on Symmetry (R) C(18) column. Quantitation was achieved using ESI-interface employing MRM mode. Results: The method was validated over the concentration range of 0.5-30 mu g/m1 (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 different conditions showed that the drug was stable under the studied conditions. Matrix effect study showed a lack of matrix effect on mass ions of TPM and IS. Conclusion: The described method compared well when assessed by Heathcontrol TDM theme program (r>0.99). The 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. (C) 2010 Elsevier B.V. All rights reserved.