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

• Published in: Journal of mass spectrometry. 2001-02, Vol.36 (2), p.188-194
• Main Authors: Ifa, Demian R., Falci, Márcio, Moraes, Maria E., Bezerra, Fernando A. F., Moraes, Manoel O., Nucci, Gilberto de
• Format: Article
• Language: English
• Subjects: Acetates - blood; Acetates - chemistry; Amines; Analysis; Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; chromatography; Chromatography, High Pressure Liquid; Cyclohexanecarboxylic Acids; gabapentin; gamma-Aminobutyric Acid; General pharmacology; human plasma; Humans; mass spectrometry; Medical sciences; Neuropharmacology; Pharmacology. Drug treatments; Spectrometry, Mass, Electrospray Ionization
• ISSN: 1076-5174; 1096-9888
• DOI: 10.1002/jms.120

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 C4 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 Cmax. Since both 90% CI for AUC(0–36 h) and Cmax 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.