LC-MS/MS method for determination of epothilone B in rat plasma and its application in pharmacokinetic study

摘要

Background: A simple LC-MS/MS method was developed for determination and pharmacokinetic study of Epothilone B in rat plasma. Methods: Plasma sample pretreatment involved a one-step liquid-liquid extraction of 100μL plasma. The chromatographic separation was carried out on a Agilent Zobax SB C 18 column with a mobile phase consisting of 10mmol/L ammonium acetate-acetonitrile (35:65, v/v) at a flow rate of 0.2mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by SRM via electro spray ionization source with positive mode. Results: The standard curve for Epothilone B was linear over the concentration range of 1-100ng/mL with a lower limit of quantification of 0.5ng/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; AUC 0-24h, 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. Conclusion: 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.