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 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.

Validated LC‐MS/MS method for quantification of gabapentin in human plasma: application to pharmacokinetic and bioequivalence studies in Korean volunteers

“…Because the inherent selectivity of MS/MS method was beneficial in developing a selective and sensitive analytical methodology for trace-mixture analysis (Jemal, 2000), it was necessary to use MS/MS detection for GB level in plasma below the reported lowest LLOQ (40 ng/mL; Ramakrishna et al, 2006;Ifa et al, 2001;Ji et al, 2006). The molecular structures of GB and IS are shown in Fig.…”

“…However, most of these methods need to complicated sample preparation such as derivatization, protein precipitation or solid-phase extraction, and are thus laborious and time-comsuming. Recently, sensitive methods for GB determination in serum using GC/tandem mass spectrometry (MS/MS) (Gambelunghe et al, 2005) or LC-MS/MS (Ramakrishna et al, 2006;Ifa et al, 2001;Ji et al, 2006) based on protein precipitation without a derivatization step have been reported.…”

Modern Methods for Analysis of Antiepileptic Drugs in the Biological Fluids for Pharmacokinetics, Bioequivalence and Therapeutic Drug Monitoring

“…The method most commonly used for GBP quantification in blood or serum is reversed-phase HPLC with derivatization and fluorometric detection [146][147][148]. GC methods have also been reported [149], and more recently, more sensitive and validated LC procedures with MS or MS/MS methods for both clinical and experimental monitoring of GBP in human and animal have been also been described [149][150][151][152][153].…”

Kinetic and Thermodynamic Spectrophotometric Technique to Estimate Gabapentin in Pharmaceutical Formulations using Ninhydrin

“…Its action is attributed to the irreversible inhibition of the enzyme GABA-transaminase, thus preventing the physiological degradation of GABA in the brain (Ouellet et al 2001). Analytical methods reported for its determination consist of high-performance liquid chromatography (HPLC) (Jiang & Li 1999;Tang et al 1999;Chollet et al 2000;Ifa et al 2001;Ratnaraj & Patsalos 1998;Wad & Kramer 1998), spectrofluorimetry (Belal et al 2002;Hassan et al 2001), gas chromatography-mass spectrometry (GC-MS) (Kushnir et al 1999;Van Lentea & Gatautis 1998), capillary electrophoresis (Rada et al 1998) and spectrophotometry applying Hantzsch reaction (al-Zehouri et al 2001). So far, no traces of any attempts have been found for determination of gabapentin by colorimetric method and the literature is still starving for such analytical procedures.…”