A rapid and sensitive UHPLC–MS/MS method for quantification of 83b1 in plasma and its application to bioavailability study in rats

Dingsheng Wen, Jing Guo, Fulin Jiang, Caishun Huang, Zhenzhen Zhao, Gui Lu, Jiangying Chen, Liuyun Qin, Zhangwei Li, Xueding Wang, Zhuoan Deng, Min Huang, Chan Albert Sun Chi, Tang Johnny Cheuk On, Guoping Zhong

Research output: Journal article publicationJournal articleAcademic researchpeer-review

Abstract

Great attentions have been drawn by quinoline for its broad bioactivity as anti-fungal, anti-bacterial and anti-tumor activities. Compared with cisplatin, 83b1, a quinoline derivative, showed equal activity in anti-tumor and lower cyctotoxicity in normal cell. In this study, a simple, rapid and sensitive method for determination of 83b1 in rat plasma using UHPLC–MS/MS was developed for the first time. Loratadine was used as an internal standard (IS). Separation was performed on an Xterra MS C18column by isocratic elution using acetonitrile: water solution with 1‰ formic acid (90:10, v/v) as mobile phase at a flow rate of 0.3 mL/min. A triple quadrupole mass spectrometer operating in the positive ion-switching electron spray ionization mode with selection reaction monitoring (SRM) was employed to determine 83b1 and IS transitions of m/z 321.82 → 147.84, 382.71 → 258.76 for 83b1 and Loratadine, respectively. The values of specificity, linearity and lower limit of quantification, intra- and inter- day precision and accuracy, extraction recovery, matrix effect and stability for this method satisfied the acceptable limits. The lower limit of quantification was 0.5 ng/mL with a linear range of 0.5–1500 ng/mL. The validated method was employed to study the bioavailability of 83b1 in rat by dosing with intravenous injection (1 mg/kg) and gavage (10 mg/kg), and the oral bioavailability of 83b1 in rat was calculated as 20.9 ± 8.8%.
Original languageEnglish
Pages (from-to)71-76
Number of pages6
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume134
DOIs
Publication statusPublished - 5 Feb 2017

Keywords

  • 83b1
  • Bioavailability
  • Method validation
  • UHPLC–MS/MS

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

Cite this