title: A rapid and sensitive UHPLC-MS/MS method for quantification of 83b1 in plasma and its application to bioavailability study in rats.
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 0.3mL/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 0.5ng/mL with a linear range of 0.5-1500ng/mL. The validated method was employed to study the bioavailability of 83b1 in rat by dosing with intravenous injection (1mg/kg) and gavage (10mg/kg), and the oral bioavailability of 83b1 in rat was calculated as 20.9±8.8%.
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-Sen University, No.74, 2nd Yat-Sen Road, Yuexiu District, Guangzhou City, Guangdong Province 510080, China. Electronic address: dswen168@163.com.
authors.forename: Dingsheng
authors.initials: D
authors.lastname: Wen
authors.affiliation: Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan Road East, Guangzhou City, Guangdong Province 510006, China. Electronic address: 1043397061@qq.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Guo
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-Sen University, No.74, 2nd Yat-Sen Road, Yuexiu District, Guangzhou City, Guangdong Province 510080, China. Electronic address: jflzd163@163.com.
authors.forename: Fulin
authors.initials: F
authors.lastname: Jiang
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-Sen University, No.74, 2nd Yat-Sen Road, Yuexiu District, Guangzhou City, Guangdong Province 510080, China. Electronic address: 549567264@qq.com.
authors.forename: Caishun
authors.initials: C
authors.lastname: Huang
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-Sen University, No.74, 2nd Yat-Sen Road, Yuexiu District, Guangzhou City, Guangdong Province 510080, China. Electronic address: yqnlcc77@126.com.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan Road East, Guangzhou City, Guangdong Province 510006, China. Electronic address: lugui@mail.sysu.edu.cn.
authors.forename: Gui
authors.initials: G
authors.lastname: Lu
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-Sen University, No.74, 2nd Yat-Sen Road, Yuexiu District, Guangzhou City, Guangdong Province 510080, China. Electronic address: chenjiangying222@163.com.
authors.forename: Jiangying
authors.initials: J
authors.lastname: Chen
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-Sen University, No.74, 2nd Yat-Sen Road, Yuexiu District, Guangzhou City, Guangdong Province 510080, China.
authors.forename: Liuyun
authors.initials: L
authors.lastname: Qin
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-Sen University, No.74, 2nd Yat-Sen Road, Yuexiu District, Guangzhou City, Guangdong Province 510080, China. Electronic address: 395024754@qq.com.
authors.forename: Zhangwei
authors.initials: Z
authors.lastname: Li
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-Sen University, No.74, 2nd Yat-Sen Road, Yuexiu District, Guangzhou City, Guangdong Province 510080, China. Electronic address: wangxd@mail.sysu.edu.cn.
authors.forename: Xueding
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Chirosciences, Lo Ka Chung Centre for Natural Anti-cancer Drug Development, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China.
authors.forename: Zhuoan
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-Sen University, No.74, 2nd Yat-Sen Road, Yuexiu District, Guangzhou City, Guangdong Province 510080, China. Electronic address: huangmin@mail.sysu.edu.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.affiliation: Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan Road East, Guangzhou City, Guangdong Province 510006, China. Electronic address: chenxz3@mail.sysu.edu.cn.
authors.forename: Chan Albert Sun
authors.initials: CAS
authors.lastname: Chi
authors.affiliation: State Key Laboratory of Chirosciences, Lo Ka Chung Centre for Natural Anti-cancer Drug Development, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China. Electronic address: dr-johnny.tang@polyu.edu.hk.
authors.forename: Tang Johnny Cheuk
authors.initials: TJC
authors.lastname: On
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, North Campus, Sun Yat-Sen University, No.74, 2nd Yat-Sen Road, Yuexiu District, Guangzhou City, Guangdong Province 510080, China. Electronic address: zhonggp@mail.sysu.edu.cn.
authors.forename: Guoping
authors.initials: G
authors.lastname: Zhong
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D008297:Male; D011804:Quinolines / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000970:Antineoplastic Agents; D011804:Quinolines
keywords: 83b1; Bioavailability; Method validation; UHPLC–MS/MS