A specific and sensitive liquid chromatography-electrospray ionization tandem mass spectrometry method was developed for the determination of zolmitriptan in human plasma. Zolmitriptan and the internal standard (IS) rizatriptan were extracted by liquid–liquid extraction and were separated on a sunfire C18 column (100 x 2.1mm and 3.5µm) with isocratic elution of mobile phase consisting of 10mM ammonium formate containing 0.1% formic acid and acetonitrile. Electrospray ionization in multiple reaction monitoring mode was used to monitor the parent and the daughter ions of the analyte and the internal standard. The response is linear over a range of 0.5 to 100.0 ng/ml concentration with a correlation coefficient (r2) greater than 0.99 and an extraction efficiency of about 95%. The validated method can be applied to pharmacokinetic, toxicokinetic and bioequivalence studies.