质谱联用法研究奥克梯隆型皂苷元在大鼠体内的药代动力学行为

Pharmacokinetic Study of Ocotillol in Rats by LC-MS/MS

目的建立测定大鼠血浆中奥克梯隆型皂苷元奥克梯隆(ocotillol)浓度的LC-MS/MS检测方法,研究其在大鼠体内的药动学行为。方法血浆样品采用甲醇沉淀蛋白法进行提取,通过LC-MS/MS分析测定单剂量灌胃给予ocotillol后大鼠血浆样品中的药物浓度,获得药-时曲线并计算药动学参数。结果 Ocotillol在10~240 ng·m L^(-1)内呈现良好的线性关系,质控样品的日内和日间精密度(RSD)均小于15%,方法回收率均高于84.14%;大鼠灌胃给予40 mg·kg-1ocotillol后,平均血药浓度-时间曲线出现了双峰现象,ocotillol在大鼠体内的t1/2为(8.82±7.56)h,tmax为(0.83±0.26)h,ρmax为(156.60±51.84)ng·m L^(-1),AUC0-t为(687.15±144.08)ng·h·m L^(-1)。结论 Ocotillol口服后吸收快,消除慢,吸收入血较少,且该化合物在体内吸收代谢可能存在肠肝循环。

OBJECTIVE To develop an LC-MS/MS method for the quantitative analysis of ocotillol in rat plasma, and study the pharmacokinetic characteristics of ocotillol in rats after oral administration.METHODS Ocotillol was extracted from plasma sample by protein precipitation. The concentration of ocotillol in plasma was determined by LC-MS/MS and the plasma concentration-time curve and main pharmacokinetic parameters were calculated after a single oral administration of ocotillol at 40 mg·kg^-1 to SD rats.RESULTS Excellent linearity was found between 10-240 ng·mL^-1. Intra-and inter-day precision values （RSDs） of QC samples were both below 15% and the extraction recoveries of ocotillol from plasma were higher than 84.14%. Double peaks were observed in the mean plasma concentration versus time profile of ocotillol after oral administration. The main pharmacokinetic parameters of ocotillol were as follows：the mean maximum plasma concentration （ρmax） was （156.60±51.84） ng·mL^-1 occurring at （0.83±0.26） h post dose, the mean elimination half-time （t1/2） was （8.82±7.56） h, and the mean area under the plasma concentration versus time curve （AUC0-t） was （687.15±144.08） ng·h·mL^-1.CONCLUSION The current data shows that ocotillol is rapidly absorbed in rats after oral administration and slowly eliminated from circulatory blood system, with low plasma exposure. Enterohepatic circulation may contribute to the atypical drug absorption profiles.