Gabapentin quantification in human plasma by high‐performance liquid chromatography coupled to electrospray tandem mass spectrometry. Application to bioequivalence study

Abstract A rapid, sensitive and specific analytical method was developed and validated to quantify gabapentin in human plasma using acetaminophen as an internal standard. The method employs a single plasma protein precipitation. The analytes are chromatographed on a C 4 reversed‐phase chromatographic column and analyzed by mass spectrometry in the multiple reaction monitoring (MRM) mode. The method has a chromatographic run time of 4 min and a linear calibration curve over the range 50–10 000 ng ml −1 ( r > 0.999). The between‐run precision, based on the relative standard deviation for replicate quality controls, was ≤4.8 % (200 ng ml −1 ), 6.0% (1000 ng ml −1 ) and 4.4% (5000 ng ml −1 ). The between‐run accuracy was ±2.6, 4.4 and 0.5% for the above‐mentioned concentrations, respectively. This method was employed in a bioequivalence study of two gabentin capsule formulations (Progresse from Biosintética, Brazil, as a test formulation, and Neurotin from Parke‐Davis, as a reference formulation) in 24 healthy volunteers of both sexes who received a single 300 mg dose of each formulation. The study was conducted using an open, randomized, two‐period crossover design with a 7‐day washout interval. The 90% confidence interval (CI) of the individual ratio geometric mean for Progresse/Neurotin was 87.9–115.6% for AUC (0–36 h) and 88.6–111.7% for C max . Since both 90% CI for AUC (0–36 h) and C max were included in the 80–125% interval proposed by the US Food and Drug Administration, Progresse was considered bioequivalent to Neurotin according to both the rate and extent of absorption. Copyright © 2001 John Wiley & Sons, Ltd.