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Quantitation of bentysrepinine (Y101) in rat plasma by liquid chromatography tandem mass spectrometry: Application to pharmacokinetic study

Author:
Fan, Huirong, Li, Ruixing, Gu, Yuan, Si, Duanyun, Liu, Changxiao
Source:
Journal of chromatography 2012 v.889-890 pp. 103-109
ISSN:
1570-0232
Subject:
formic acid, ionization, liquid chromatography, methanol, monitoring, pharmacokinetics, rats, spectrometers, storage time, tandem mass spectrometry
Abstract:
A simple, accurate and sensitive liquid chromatography tandem mass spectrometry (LC–MS/MS) method was developed and validated for quantitation of bentysrepinine (Y101) in rat plasma. After the addition of diphenhydramine (internal standard, IS), plasma samples were pretreated by protein precipitation. Chromatographic separation was carried out on an Atlantis® analytical column (4.6mm×100mm, 5μm, Waters) with methanol: 20mM ammonium formate consisting of 1.0% formic acid (65:35, v/v) as the mobile phase at an isocratic flow rate of 0.4mL/min for 7.5min. The multiple reaction monitoring (MRM) transitions were performed at m/z 490.2→339.5 for Y101and m/z 256.0→167.0 for IS on a SCIEX API 4000 mass spectrometer in the positive ion mode with electrospray ionization (ESI) source. Good linearity was achieved over the concentration range of 1–2500ng/mL. The intra- and inter-day precisions were less than 8.3%, and the accuracy ranged from −4.0% to 2.8%. Y101 was stable during the analysis and the storage period. The pharmacokinetic profiles of Y101 at three dose levels were successfully studied for the first time in rats by this method. After single intra-gastric administration of Y101 at the doses of 25, 50 and 100mg/kg, Cₘₐₓ and AUC₀–ₜ were proportional to the doses given.
Agid:
1004009