A simple and accurate liquid chromatography-tandem mass spectrometry method for quantification of zonisamide in plasma and its application to a pharmacokinetic study. 
Zonisamide (ZNM) is an antiepileptic drug that is used as an adjunctive therapy in the treatment of adults with partial seizures.  An LC-MS/MS method for quantification of ZNM in human and rabbit plasma using (2)H4,(15)N-Zonisamide as an internal standard (IS) has been developed and validated.  The drug and IS were extracted by ether and analyzed on Symmetry(®) C18 column.  Quantitation was achieved using ESI-interface employing MRM mode.  The method was validated over the concentration range of 0.5-50μg/mL and 0.5-30μg/mL (r(2)>0.99) in human and rabbit plasma samples, respectively.  Intra- and inter-run precision of ZNM assay in human and rabbit plasma samples ranged from 0.8 to 8.5% with accuracy (bias) varied from -11.3 to 14.4% indicating good precision and accuracy.  Stability of ZNM in human and rabbit plasma samples at various conditions showed that the drug was stable under the studied conditions.  Analytical recoveries of ZNM and IS from spiked human and rabbit plasma samples were in the range of 70.8-77.3% and 85.6-110.4%, respectively.  Matrix effect study showed a lack of matrix effect on mass ions of ZNM and IS.  The developed method was successfully applied for a pharmacokinetic study by measuring ZNM in rabbit plasma samples.  Moreover, the method is routinely utilized for TDM of ZNM.