title: The absolute bioavailability investigation of LS177 in rats using ultra-performance liquid chromatography-tandem mass spectrometry.
abstract: LS177 is a novel inhibitor of mesenchymal epithelial transition (MET) that was used as an anticancer agent. The present study was to evaluate the absolute bioavailability of LS177 in rats. A rapid and sensitive ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS/MS) method has been developed and validated for the determination of LS177 in rat plasma. LS177 and internal standard (IS, LS410) were extracted from rat plasma samples by protein precipitation (PPT) for intravenous group and liquid-liquid extraction (LLE) procedure for oral group, then separated on a Phenomenex Kinetex XB-C18 (2.1 mm I.D. × 50 mm, 2.6 µm) using a mobile phase consisting of 0.1% formic acid in acetonitrile-0.1% formic acid water with a gradient elution program. The standard curves were linear over the ranges of 5.0-2000.0 ng · mL(-1) for PPT and 1.0-200.0 ng · mL(-1) for LLE. The mean recovery of LS177 was greater than 83.4% for PPT and not less than 88.5% for LLE, respectively. The intra- and inter-day accuracy and precision were within the acceptable limits of less than 15.0% at all concentrations. The validated method was successfully applied to the bioavailability study in rat plasma of LS177 and its absolute bioavailability was 25.37%.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Lunhui
authors.initials: L
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ju
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Feifei
authors.initials: F
authors.lastname: Zhou
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Simin
authors.initials: S
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Kaishun
authors.initials: K
authors.lastname: Bi
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Chen
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D057230:Limit of Detection; D059625:Liquid-Liquid Extraction; D008297:Male; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000097:blood*; D019859:Proto-Oncogene Proteins c-met / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D047428:Protein Kinase Inhibitors; D019859:Proto-Oncogene Proteins c-met
keywords: bioavailability; ls177; met inhibitor; ultra hplc-ms/ms