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.
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.
Chang
Yi-Wei
YW
Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35, Keyan Road, Zhunan Town, Miaoli County, Taiwan, ROC.
Chen
Wei-Cheng
WC
Lin
Ke-Ta
KT
Chang
Ling
L
Yao
Hsien-Tsung
HT
Hsieh
Hsing-Pang
HP
Lan
Shih-Jung
SJ
Chen
Chiung-Tong
CT
Chao
Yu-Sheng
YS
Yeh
Teng-Kuang
TK
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*
C488735:6-methoxy-3-(3',4',5'-trimethoxybenzoyl)-1H-indole; D007211:Indoles