秋水仙碱缓释微丸在大鼠体内的药代动力学研究  

Pharmacokinetics of colchicine sustained-release pellets in rats

作　　者：张楠[1] 张宇佳[1] 魏曼[1] 宋辉 方夏琴 郑稳生[1] 

机构地区：[1]北京协和医学院中国医学科学院药物研究所药物传输技术及新型制剂北京市重点实验室,北京100050

出　　处：《中南药学》2017年第12期1695-1699,共5页Central South Pharmacy

摘　　要：目的建立LC-MS法测定SD大鼠血浆中秋水仙碱浓度,并比较灌胃含药量0.572 mg·kg^(-1)的秋水仙碱片剂和自制秋水仙碱缓释微丸的药代动力学,考察秋水仙碱缓释微丸的释药特性。方法血浆样品以替加氟为内标,经乙酸乙酯沉淀蛋白后进行LC-MS分析。采用高效液相色谱分离系统,色谱柱为Durashell C_(18)(2.1 mm×50 mm,3μm);流动相为甲醇-10 mmol·L^(-1)乙酸铵溶液(45∶55,v/v);采用质谱检测系统,ESI离子源,正离子模式,选择离子检测(SIM)方式,定量分子离子为秋水仙碱[M+H]^+:400.2,替加氟[M+H]^+:201.1。结果秋水仙碱质量浓度在0.05~15 ng·mL^(-1)内与峰面积线性关系良好,定量限为0.05 ng·mL^(-1)。绝对回收率为73.60%~77.24%,相对回收率为91.3%~101.7%,日间精密度≤2.1%,日内精密度≤2.5%。结论本方法简单快速,灵敏准确,适用于秋水仙碱在大鼠体内的药代动力学研究。所制缓释微丸能够平稳血药浓度,延长释药时间,具有良好的缓释效果。Objective To establish a rapid, sensitive, simple, and economical analytical method to characterize the pharmacokinetic profiles of sustained releasing pellets （SRPs） of colchicine. Methods The concentration of colchicine in the plasma of Sprague-Dawley rats was quantified via a liquid chromatography-tandem mass spectrometry （LC-MS） method. The pharmacokinetic profiles of tablets and SRPs of colchicine （0.572 mg·kg-1） were compared after the intragastric administration. The blood samples obtained from the rats were analyzed by LC-MS method with the internal standard of tegafur after protein precipitation with ethyl acetate. The analytes were isolated with a Durashell C18 column （2.1 mm ~ 50 mm, 3 μm ） after positive ionization. Ions （[M ＋ H]＋400.2 and [M ＋ H] ＋201.1） were monitored via a monitoring mode of selected ions （SIM）. Results Good colchicine linearity was shown at 0.05 - 15 ng · mL - 1 with a lower limit of quantification at （0.05 ng ·mL -1）. The absolule recovery was 73.60% - 77.24%, and the relative recovery was 91.3% -- 101.7%. The RSDs of the intra- and inter-day were less than 2.1% and 2.5%, respectively. Conclusion The method is simple and accurate. The strength form of SRPs is characterized by the LC-MS method and shows a prolonged release with stable blood concentrations and release effect.

关 键 词：秋水仙碱 缓释微丸 药代动力学 大鼠 

分 类 号：R96[医药卫生—药理学]