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

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 134; pp. 71 - 76
• Main Authors: Wen, Dingsheng, Guo, Jing, Jiang, Fulin, Huang, Caishun, Zhao, Zhenzhen, Lu, Gui, Chen, Jiangying, Qin, Liuyun, Li, Zhangwei, Wang, Xueding, Deng, Zhuoan, Huang, Min, Chi, Chan Albert Sun, On, Tang Johnny Cheuk, Zhong, Guoping
• Format: Journal Article
• Language: English
• Published: England Elsevier B.V 05.02.2017
• Subjects: 83b1; Administration, Oral; Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - blood; Antineoplastic Agents - chemistry; Bioavailability; Biological Availability; Chromatography, High Pressure Liquid - methods; Male; Method validation; Quinolines - administration & dosage; Quinolines - blood; Quinolines - chemistry; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry - methods; UHPLC–MS/MS; Cmax; COX-2; Method validation; F; UHPLC–MS/MS; CL; Bioavailability; MTS; ESCC; MTBE; Vd; MRT; SRM; AUC; PGH; 83b1; CDDP; QC; PPAR; t1/2; Tmax; AUC0–t
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2016.11.011

•The compound 83b1 has the potential to develop as a novel anti- esophageal cancer drug for its high anti-tumor activity and low cytotoxicity.•[J1] A simple, rapid and sensitive method for determination of 83b1 in rat plasma using UHPLC–MS/MS was developed and validated for the first time.•The validated method was employed to study the bioavailability of 83b1 in rat by dosing with intravenous injection (1mg/kg) and gavage (10mg/kg). 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 C18 column 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%.