title: Quantitation of bentysrepinine (Y101) in rat plasma by liquid chromatography tandem mass spectrometry: application to pharmacokinetic study.
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 (4.6 mm × 100 mm, 5 μm, Waters) with methanol: 20 mM ammonium formate consisting of 1.0% formic acid (65:35, v/v) as the mobile phase at an isocratic flow rate of 0.4 mL/min for 7.5 min. The multiple reaction monitoring (MRM) transitions were performed at m/z 490.2→339.5 for Y101 and 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 1-2500 ng/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 100 mg/kg, C(max) and AUC(0-t) were proportional to the doses given.
authors.affiliation: Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Huirong
authors.initials: H
authors.lastname: Fan
authors.forename: Ruixing
authors.initials: R
authors.lastname: Li
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gu
authors.forename: Duanyun
authors.initials: D
authors.lastname: Si
authors.forename: Changxiao
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D001549:Benzamides / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods*; D004151:Dipeptides / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D008297:Male; D010936:Plant Extracts / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000998:Antiviral Agents; D001549:Benzamides; D004151:Dipeptides; C573540:N-(N-benzoyl-O-(2-dimethylaminoethyl)tyrosyl)phenylalaninol; D010936:Plant Extracts