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Background: Published methods for routine clinical monitoring of vigabatrin and gabapentin are often very laborious. A simple GC-MS method was developed for the simultaneous quantitative determination of vigabatrin and gabapentin in human serum., Methods: After protein precipitation, the compounds are derivatized by methylation and analysed on a polydimethylsiloxane column using splitless injection. Cyclobarbital is used as the internal standard. To attain maximal sensitivity, detection is performed in selected ion monitoring mode., Results: The method was fully validated and linear calibration curves were obtained in the concentration ranges from 5 to 80 microg/mL for vigabatrin and from 5 to 30 microg/mL for gabapentin. The within-day and day-to-day relative standard deviations at three different concentration levels were <10% and <15%, respectively. The limit of quantitation was 2 mug/mL for both compounds., Conclusions: The presented method provides high chromatographic resolution, good sensitivity and unequivocal identification potential and can be used for simultaneous analysis of both antiepileptics.