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Determination of aniracetam's main metabolite, N-anisoyl-GABA, in human plasma by LC–MS/MS and its application to a pharmacokinetic study

Cai, Shuang, Wang, Lei
Journal of chromatography 2012 v.897 pp. 50-54
abscisic acid, acetates, high performance liquid chromatography, humans, ionization, metabolites, methanol, monitoring, oral administration, pharmacokinetics, spectrometers, tandem mass spectrometry
A simple and rapid high-performance liquid chromatography–electrospray ionization tandem mass spectrometry (LC–ESI-MS/MS) method has been developed and validated for the determination of 4-p-anisamidobutyric acid (ABA; or N-anysoyl-γ-aminobutiryc acid, N-anisoyl-GABA), a major active metabolite of aniracetam, in human plasma. After protein precipitation of plasma sample with methanol, ABA and the internal standard lisinopril were separated on a Venusil ASB C₁₈ column at 25°C. The mobile phase consisted of methanol–ammonium acetate (10mmol/L) (30:70, v/v). The detection was performed on a triple quadrupole tandem mass spectrometer with an ESI source in negative ion mode. Multiple reaction monitoring (MRM) using the precursor→product ion combinations of m/z 235.8→m/z 106.6, and m/z 403.8→m/z 113.6 was used to quantify ABA and lisinopril, respectively. This is the first LC–MS/MS method for ABA with advantages of short analysis time (4.5min per sample run) and high selectivity attributable to the MRM detection and optimized HPLC conditions. The response was linear in a concentration range of 0.0485–19.4μg/mL in plasma. The extraction recovery of ABA was between 89.1% and 100.7%. The precision (RSD) and accuracy (RE) of the method were evaluated to be within 7.3% and from 2.5% to 6.9%. The validated method has been applied to the pharmacokinetic study after a single oral administration of aniracetam dispersible tablets to human beings.