title: Development and validation of a liquid chromatography-tandem mass spectrometry for the determination of BPR0L075, a novel antimicrotuble agent, in rat plasma: application to a pharmacokinetic study.
abstract: A rapid and sensitive liquid chromatography-tandem mass spectrometric method (LC-MS/MS) had been developed and validated to determine the concentrations of BPR0L075 in rat plasma. After a simple protein precipitation of plasma samples by acetonitrile, BPR0L075 was analyzed on a C(8) column at a flow rate of 0.5 mL/min. The mobile phase consisted of a mixture of 10 mM ammonium acetate containing 0.1% formic acid and acetonitrile (20:80, v/v). Both BPR0L075 (analyte) and the internal standard (BPR0L092) were determined using electro-spray ionization and the MS data acquisition was via multiple reactions monitoring (MRM) in positive scanning model. The MS/MS ion transitions monitored are m/z 342.2/195.2 and 312.5/165.2 for BPR0L075 and BPR0L092, respectively. The low limit of quantitation was 0.5 ng/mL. Each plasma sample was chromatographed within 5 min. The method was validated with respect to linearity, accuracy, precision, recovery, and stability. A good linear relationship was observed over the concentration range of 0.5-1000 ng/mL (r>0.9994). Absolute recoveries ranged from 63.45 to 68.34% in plasma at the concentrations of 2, 40, 400, and 800 ng/mL. The intra- and inter-day accuracy ranged from 92.04 to 111.80%. Intra- and inter-day relative standard deviations were 1.08-3.29% and 1.96-5.46%, respectively. This developed and validated assay method had been successfully applied to a pharmacokinetic study after intravenous injection of BPR0L075 in rats at a dose of 5mg/kg.
authors.affiliation: Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35, Keyan Road, Zhunan Town, Miaoli County, Taiwan, ROC.
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Chang
authors.forename: Wei-Cheng
authors.initials: WC
authors.lastname: Chen
authors.forename: Ke-Ta
authors.initials: KT
authors.lastname: Lin
authors.forename: Ling
authors.initials: L
authors.lastname: Chang
authors.forename: Hsien-Tsung
authors.initials: HT
authors.lastname: Yao
authors.forename: Hsing-Pang
authors.initials: HP
authors.lastname: Hsieh
authors.forename: Shih-Jung
authors.initials: SJ
authors.lastname: Lan
authors.forename: Chiung-Tong
authors.initials: CT
authors.lastname: Chen
authors.forename: Yu-Sheng
authors.initials: YS
authors.lastname: Chao
authors.forename: Teng-Kuang
authors.initials: TK
authors.lastname: Yeh
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D007211:Indoles / Q000097:blood* / Q000493:pharmacokinetics / Q000494:pharmacology; D008938:Mitosis / Q000187:drug effects*; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C488735:6-methoxy-3-(3',4',5'-trimethoxybenzoyl)-1H-indole; D007211:Indoles