Validated LC-MS/MS method for quantification of gabapentin in human plasma: application to pharmacokinetic and bioequivalence studies in Korean volunteers.
A sensitive validated liquid chromatography-tandem mass spectrometric method (LC-MS/MS) for gabapentin (GB) in human plasma has been developed and applied to pharmacokinetic (PK) and bioequivalence (BE) studies in human. In a randomized crossover design with a 1-week period, each subject received a 300 mg GB capsule. The procedure involves a simple protein precipitation with acetonitrile and separated by LC with a Gemini C(18) column using acetonitrile-10 mm ammonium acetate (20:80, v/v, pH 3.2) as mobile phase. The GB and internal standard [(S)-(+)-alpha-aminocyclohexanepropionic acid hydrate] were analyzed using an LC-API 2000 MS/MS in multiple reaction monitoring mode. The ionization was optimized using ESI(+) and selectivity was achieved using MS/MS analysis, m/z 172.0 --> 154.0 and m/z 172.0 --> 126.0 for GB and IS, respectively. The assay exhibited good linearity over a working range of 20-5000 ng/mL for GB in human plasma with a lower limit of quantitation of 20 ng/mL. No endogenous compounds were found to interfere with the analysis. The accuracy and precision were shown for concentrations over the standard ranges. This method was successfully applied for the PK and BE studies by analysis of blood samples taken up to 36 h after an oral dose of 300 mg of GB in 24 healthy volunteers.
Park
Jin-Hee
JH
Department of Pharmacology and Institute of Biomedical Sciences, College of Medicine, Hanyang University, Seoul 133-791, South Korea.
Jhee
Ok-Hwa
OH
Park
Song-Hee
SH
Lee
Jung-Sik
JS
Lee
Min-Ho
MH
Shaw
Leslie M
LM
Kim
Kwang-Hyun
KH
Lee
Jong-Ho
JH
Kim
Yong-Seok
YS
Kang
Ju-Seop
JS
D000284:Administration, Oral; D000588:Amines / Q000097:blood* / Q000493:pharmacokinetics; D000927:Anticonvulsants / Q000097:blood* / Q000493:pharmacokinetics; D001274:Atmospheric Pressure; D018592:Cross-Over Studies; D003509:Cyclohexanecarboxylic Acids / Q000097:blood* / Q000493:pharmacokinetics; D000077206:Gabapentin; D006801:Humans; D012015:Reference Standards; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013810:Therapeutic Equivalency; D005680:gamma-Aminobutyric Acid / Q000097:blood* / Q000493:pharmacokinetics
D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin