High-Throughput Analytic Method Development for Gabapentin in Human Plasma by LC Coupled with Tandem Mass Spectrometry for Pharmacokinetic Studies

다국어 초록 (Multilingual Abstract)

A simple, sensitive and validated liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) for gabapentin (GBP) in human plasma has been developed for pharmacokinetic (PK) studies. In a single-dose PK study of GBP in normal 24 subjects were given single oral doses of 300 mg GBP after fasting 12 hours. Plasma samples were drawn predose and then serially at 13 times after dose for 36 hours and plasma GBP were analyzed by deveopled LC-MS/MS. The procedures involves a simple protein precipitation with acetonitrile (ACN) and separated by LC equipped with C18 column using ACN: 10 mM ammonium acetate (20:80, v/v, pH adjusted to 3.2 with acetic acid) as mobile phase. The GBP and α-aminocyclohexane propionic acid hydrate (IS, internal standard) were analyzed by API 2000 MS/MS in the multiple-reaction monitoring (MRM) mode. The MS/MS analysis was optimized using ESI (+) and selectivity with ionization as m/z 154.0 for GBP and m/z 126.0 for IS that fully separated during a 4.0-min run time. The accuracy and precision were met the analytical method validation criteria for concentrations over the standard ranges. The calibration curve was linear over a working range of 20(LLOQ) - 5,000 ng/ml and no interfering endogenous compounds with the analysis. This LC-MS/MS method was successfully applied for the GBP PK studies after single oral dosing of 300 mg of GBP in 24 Korean healthy subjects. (Cancer Prev Res 12, 41-50, 2007)

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