摘要
目的建立人血浆中石杉碱甲浓度的HPLGM9MS测定法，研究2种石杉碱甲片在正常人体的相对生物利用度。方法以盐酸伪麻黄碱为内标，血浆样品经乙酸乙酯萃取，汉邦C18柱（4．6mm×150mm，5μm）分离后，采用HPLC-MS-MS联用法检测，18名健康男性志愿者采用双周期随机交叉试验设计，分别单剂量口服石杉碱甲片（T或R）0．2mg后测定两者的相对生物利用度。结果石杉碱甲与内标分离度好，内源性杂质不干扰测定，在0．0508～5．080μg·L^-1（r=0．9998）石杉碱甲浓度与峰面积比的线性关系良好，定量限为0．0508μg·L^-1，回收率为101．8％～109．8％（n=5），日内RSD为1．8％～3．9％（n=5）；日间RSD为2．3％～8．7％（n=15）。单次服用0．2mg石杉碱甲片后T与R的AUC0～24分别为（16．35±3．42）μg·h·L^-1和（16．38±3．61）μg·h·L^-1；AUC0-∞分别为（17．53±3．80）μg·h·L^-1和（17．70±3．97）μg·h·L^-1；Gmax分别为（2．47±0．49）μg·L^-1和（2．514-_0．51）μg·L^-1；tmax分别为（1．3±0．4）h和（1．2±0．3）h；t1／2分别为（5．9±0．8）h和（6．2±0．7）h。与R相比，T的相对生物利用度为100．5％±10．1％。结论该方法准确度高，灵敏度好，可用于石杉碱甲人体内过程研究。方差分析结果表明2种制剂的主要药动学参数之间无明显差异，双单侧t检验结果表明2种制剂为生物等效制剂。
Objective To establish an HPLC-MS-MS method for the determination of huperzine A in the plasma and to study the relative bioavailability and the pharmacokinetics of huperzine A tablets. Methods With pseudoephedrine hydrochloride as the internal standard, huperzine A was extracted from the plasma sample with acetic ether and analyzed by a Han Bang C18 column （4.6 mm×150 mm, 5μm）. HPLC-MS-MS was carried out with a mobile phase consisting of methanol-0. 2% methanoic acid （85 ： 15, v/v） at a flow rate of 0. 7 mL ·min^-1. A single oral dose of 0. 2 rag huperzine A （T or R） was administered to 18 healthy volunteers in a randomized crossover study. Huperzine A concentration in the plasma was determined by the newly developed HPLC-MS-MS method, and the pharmacokinetics and bioavailability were studied. Results The calibration curve was linear within 0. 0508-5. 080 μg·L^-1 （r=0. 999 8）. The method recovery of huperzine A was 101.8%-109. 8% （n=5）, and the intraday and inter-day RSD 1.8%-4.8%（n=5）, and 2.3%-8.7% （n=15）, respectively. The AUC0-24 of the two tablets was （16.35±3.42）μg . h . L^-1 and （16.38±3.61）μg. h. L^-1, Cmax was （2.47±0.49） μg. L^-1 and （2.51±0.51） μg. L^-1, and tmax was （1.3±0.4） h and （1.2±0.3） h. The relative bioavailability of T to R was 100.5%±10. 1%. Conclusion The established HPLC-MS-MS method is accurate and sensible. It can be used to study the pharmacokineties of huperzine A. There is no significant difference between the two tablets, and they are bioequivalent.
出处
《中南药学》
CAS
2009年第8期583-586,共4页
Central South Pharmacy
