title: Preclinical pharmacokinetic evaluation of a new formulation of a bifendate solid dispersion using a supercritical fluid chromatography-tandem mass spectrometry method.
abstract: In order to evaluate the pharmacokinetic characteristics of a new formulation of a bifendate solid dispersion in beagle dogs, a novel, sensitive and rapid supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS) method was established and validated. Plasma samples were subjected to liquid-liquid extraction with ethyl acetate. Separation of bifendate and diazepam (internal standard, IS) was performed on an HSS C18 SB column (3×100mm, 1.8μm) with a mobile phase consisting of CO2 (≥99.99%) - methanol (95:5, v/v) at a flow rate of 2mL/min and the compensation solvent was methanol with 2% formic acid at a flow rate of 0.2mL/min. A tandem triple quadrupole mass spectrometer was operated in multiple reaction monitoring (MRM) mode with an electrospray ionization (ESI) source. Quantification of the ion transitions was at m/z 419.2→387.0 and 284.5→193.2 for bifendate and IS, respectively. The method was sensitive with a lower limit of quantification (LLOQ) of 0.5ng/mL and linear over the concentration range 0.5-250ng/mL. All the validation data, such as precision, accuracy, extraction recovery and matrix effect, were all within acceptable criteria. The method has been successfully applied to a pharmacokinetic study of bifendate in beagle dogs after oral administration of a bifendate solid dispersion.
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Muhua
authors.initials: M
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Longshan
authors.initials: L
authors.lastname: Zhao
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Ma
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China. Electronic address: zhangth_student@aliyun.com.
authors.forename: Tianhong
authors.initials: T
authors.lastname: Zhang
mesh_terms: D000085:Acetates / Q000737:chemistry; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D001713:Biphenyl Compounds / Q000097:blood / Q000493:pharmacokinetics*; D002138:Calibration; D002626:Chemistry, Pharmaceutical; D025924:Chromatography, Supercritical Fluid / Q000592:standards; D004285:Dogs; D016903:Drug Monitoring / Q000379:methods*; D057230:Limit of Detection; D016014:Linear Models; D059625:Liquid-Liquid Extraction; D012015:Reference Standards; D015203:Reproducibility of Results; D012997:Solvents / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization / Q000592:standards; D053719:Tandem Mass Spectrometry / Q000592:standards; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D000085:Acetates; D001713:Biphenyl Compounds; D012997:Solvents; C465548:bifendate; C007650:ethyl acetate
keywords: Beagle dog plasma; Bifendate; Pharmacokinetics; SFC–MS/MS