吴茱萸碱和吴茱萸次碱在家兔体内的药动学研究

Study on Pharmacokinetics of Evodiamine and Rutaecarpine in Rabbit

目的建立家兔血浆中吴茱萸碱、吴茱萸次碱同时测定的液质联用方法,并用于口服给药后的药动学研究。方法血浆样品经甲醇沉淀除去蛋白,高效液相色谱-电喷雾质谱联用方法测定吴茱萸碱和吴茱萸次碱的血药浓度,并用3P87程序计算两者的药动学参数。结果吴茱萸碱和吴茱萸次碱分别在0．32～32．0(r=0．999 6)和1．0-40．0 μg·L-1(r=0．999 2)内呈良好线性关系,平均提取回收率在80％以上。吴茱萸碱和吴茱萸次碱的血药浓度-时间曲线均符合一室模型,曲线下面积(AUC) 分别为(183．2±76．2)和(453．5±191．0)μg·min·L-1。结论该方法简便、准确、灵敏度高,可用于家兔口服给药后吴茱萸碱和吴茱萸次碱的血药浓度测定及其药动学研究。

OBJECTIVE To establish a liquid chromatography-electmspray mass spectrometry （LC/ESI-MS） method for the determination and pharmacoldnetic study of evodiamine, mtaecarpine in rabbits. METHODS Evodiamine and mtaecarpine in rabbits plasma at different sampling time were determined by HPLC/MS. The plasma samples were depmteined by methanol. The separation was performed on an Agilent Zorbax SB-C18 column with acetonitrile-2% tetrahydorfuran （62：38） as the mobile phase at the flow rate of 0.5 mL· min^-1. Electrospray ionization source （ESI） was applied and operated in the negative ion mode. The m/z 302 （evodiamine, [M - H]^ -）, m/z 286 （rutaecarpine, [ M - H]^ - ） and 595 （mtaecarpine, [ 2M ＋ Na - 2H ]^ - ） were used to quantify evodiamine and mtaecarpine respectively using the selected ion monitoring （SIM） mode. The pharmacokinetic parameters were calculated with 3P87 pharmacokinetic program. RESULTS The lin- ear range was 0.32 - 32.0 and 1.0 - 40.0 μg · L^-1 for evodiamine and rutaecarpine, respectively. The average extraction recoveries were all over 80%. The inter- and intra-day precisions （RSD） were all less than 5% （ n = 6）. The concentration-time curves of evodiamine and rutaecarpine were fitted to an one-compartment model. The total are, as under the plasma concentration-time curve （AUC） were （183.2 ± 76.2） and （453.5 ± 191.0）μg· min· L^-1 for evodiamine and mtaecarpine, respectively.The plasma clearances （CLs） of evodiamine and mtaecarpine were （47.2 ± 29.0） and （41.4 ± 23.3 ） L· kg^-1· min^-1, re.spectively. CONCLUSION The method is simple, rapid and sensitive. It is proved to be suitable for pharmacokinetic studies of evodiamine and rutaecarpine.