Gabapentin quantification in human plasma by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry. Application to bioequivalence study.
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 x ml(-1) (r > 0.999). The between-run precision, based on the relative standard deviation for replicate quality controls, was < or = 4.8 % (200 ng x ml(-1)), 6.0% (1000 ng x ml(-1)) and 4.4% (5000 ng x 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.
Ifa
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Cartesius Analytical Unit, Department of Pharmacology, ICB-University of São Paulo, 05508-900, São Paulo, Brazil. ifa@usp.br
Falci
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Moraes
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Bezerra
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Moraes
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de Nucci
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D000085:Acetates / Q000097:blood* / Q000737:chemistry*; D000588:Amines; D002851:Chromatography, High Pressure Liquid; D003509:Cyclohexanecarboxylic Acids; D000077206:Gabapentin; D006801:Humans; D021241:Spectrometry, Mass, Electrospray Ionization; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin