关键词: 奥昔布宁, LC-MS/MS, 生物等效性, 家兔血浆, 透皮制剂

Abstract: Objective To develop and validate a LC-MS/MS method to quantify oxybutynin in rabbit plasma and evaluate the bioequivalence of self-prepared oxybutynin chloride gel and Gelnique. Methods The plasma sample was submitted to liquid–liquid extraction using methyl t-butyl ether after alkalified by 0.5mol/L NaOH, with diphenhydramine as the internal standard. Chromatographic separation was performed on a Kinetex C18 column with the mobile phase consisting of 10mmol/L ammonium acetate (1‰formic acid)–acetonitrile (50:50, v/v). Oxybutynin and diphenhydramine were ionized with an ESI source operated in positive ion mode, and the detected ions were m/z358→142 (oxybutynin)，m/z256→167(diphenhydramine). The validated method was then applied to the drug determination in rabbit plasma following single dermal topical administration of oxybutynin gel. Results Calibration curve was liner over the concentration range of 1～200 μg/L in rabbit plasma. For quality control samples, the intra- and inter-day precision was in the range of 1.67%～9.79%, and accuracy was within 92.9% to 103%. Self-prepared oxybutynin chloride gel and Gelnique were proved to be bioequivalent. Conclusions It was validated that the LC-MS/MS method is simple, strong specificity and high sensitivity, which could be successfully applied to pharmacokinetic study and bioequivalence evaluation of transdermal oxybutynin formulations in rabbit.

Key words: oxybutynin, LC-MS/MS, bioequivalence, rabbit plasma, transdermal delivery