title: LC-MS/MS method for determination of epothilone B in rat plasma and its application in pharmacokinetic study.
abstract: A simple LC-MS/MS method was developed for determination and pharmacokinetic study of Epothilone B in rat plasma.Plasma sample pretreatment involved a one-step liquid-liquid extraction of 100 µL plasma. The chromatographic separation was carried out on a Agilent Zobax SB C18 column with a mobile phase consisting of 10 mmol/L ammonium acetate-acetonitrile (35:65, v/v) at a flow rate of 0.2 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by SRM via electro spray ionization source with positive mode.The standard curve for Epothilone B was linear over the concentration range of 1-100 ng/mL with a lower limit of quantification of 0.5 ng/mL. The intra- and inter-day precision (relative standard deviation) values were not higher than 15% and the accuracy (relative error) was < 10% at 3 quality control levels. Pharmacokinetic parameters were as follows: t1/2, 3.56 (1.12) h; AUC0-24 h, 295.7 (65.3) ng · h/mL and AUC0-∞, 339.2 (87.4) ng · h/mL, CL, 5.77 (0.67) mL/h; MRT, 7.55 (2.41) h, respectively.This simple, fast and highly sensitive method was fully validated and successfully applied to a preclinical pharmacokinetic study of Epothilone B in rats after i. v. administration.
authors.affiliation: Department of Oncology, Shanghai Jiaotong University, Shanghai, China.
authors.forename: H-M
authors.initials: HM
authors.lastname: Lu
authors.forename: M
authors.initials: M
authors.lastname: Ye
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D034261:Epothilones / Q000097:blood* / Q000493:pharmacokinetics*; D005260:Female; D007202:Indicators and Reagents; D059625:Liquid-Liquid Extraction; D008297:Male; D011786:Quality Control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; D007202:Indicators and Reagents; C093788:epothilone B