Rapid quantification of gabapentin in human plasma by liquid chromatography/tandem mass spectrometry

A simple, sensitive and rapid liquid chromatography/tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of gabapentin, a new antiepileptic drug, in human plasma using its structural analogue, 1, I-cyclohexane diacetic acid monoamide (CAM) as internal standard. The method involved a simple protein precipitation by means of acetonitrile followed by a rapid isocratic elution with 10 mM ammonium formate buffer/acetonitrile (20/80, v/v, pH 3.0) on Waters Symmetry (R) C-18 reversed phase chromatographic column and analyzed by mass spectrometry in the multiple reaction monitoring mode. The precursor to product ion transitions of m/z 172 -> 154 and m/z 200 -> 182 were used to measure the analyte and the IS, respectively. The assay exhibited a linear dynamic range of 40-10 000 ng/mL for gabapentin in human plasma. The limit of detection and lower limit of quantification in human plasma were 10 and 40 ng/mL, respectively. Acceptable precision and accuracy were obtained for concentrations over the standard curve ranges. A run time of 2 min for each sample made it possible to analyze a throughput of more than 400 human plasma samples per day. The validated method has been successfully used to analyze human plasma samples for application in pharmacokinetic, bioavailability or bioequivalence studies. (c) 2005 Elsevier B.V. All rights reserved.