Determination of oxybutynin concentration in rabbit plasma by LC-MS/MS and its application to bioequivalence evaluation
- VernacularTitle:LC-MS/MS法测定家兔血浆中奥昔布宁浓度及其在生物等效性评价中的应用
- Author:
Yuan SHEN
1
;
Zhong-Jie CHEN
;
Meng-Hua ZENG
Author Information
1. 重庆医科大学附属第一医院药学部
- Keywords:
oxybutynin;
LC-MS/MS;
bioequivalence;
rabbit plasma;
transdermal delivery
- From:
Basic & Clinical Medicine
2018;38(3):324-329
- CountryChina
- Language:Chinese
-
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 0.5 mol/L NaOH, with di-phenhydramine as the internal standard. Chromatographic separation was performed on a Kinetex C18column with the mobile phase consisting of 10 mmol/L ammonium acetate(1‰formic acid)-acetonitrile(50 : 50,v/v). Oxy-butynin and diphenhydramine were ionized with an ESI source operated in positive ion mode,and the detected ions were m/z 358→142 (oxybutynin),m/z 256→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.
