中国中药杂志

2015, v.40(06) 1173-1178

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中药胃肠安丸给药后木香烃内酯及去氢木香内酯药代动力学研究
Pharmacokinetics study on costunolide and dehydrocostuslactone after administration of traditional Chinese medicine Weichang'an pills

张静泽;王磊;金兆祥;曲卓;陈钰玲;高文远;
ZHANG Jing-ze;WANG Lei;JIN Zhao-xiang;QU Zhuo;CHEN Yu-ling;GAO Wen-yuan;Special Military Drug R&D Center,Logistics University of Chinese People's Armed Police Forces;Tianjin Lerentang Pharmaceutical Factory,Tianjin Zhongxin Pharmaceuticals Group Co. ,Ltd.;School of Pharmaceutical Science and Technology,Tianjin University;

摘要(Abstract):

采用HPLC-MS/MS多反应监测(MRM)定量分析,以地西泮为内标物在正离子模式条件下建立血样中木香烃内酯(Co)及去氢木香内酯(De)药物浓度的测定方法,探讨胃肠安丸口服给药后倍半萜内酯类成分Co及De的药代动力学过程,为进一步揭示胃肠安丸抗腹泻作用的物质基础提供理论依据。血浆样品中Co在0.700 0~769.7μg·L-1,De在2.510~956.0μg·L-1线性关系良好;且精密度、稳定性及提取回收率实验结果表明该类成分血药浓度的测定方法稳定可靠。经测定口服给药后Co及De血药浓度均随给药剂量的增加而增大,Tmax在10.65~12.98 h,表明倍半萜内酯类成分血药浓度达峰值时间较晚,Co及De Cmax分别为3.750~5.450,15.34~44.52μg·L-1;Co及De在体内吸收符合一室开放模型,其体内血药浓度达峰值所需时间较长,为揭示胃肠安丸作用物质基础及指导临床用药提供实验依据。
A HPLC-MS/MS multiple-reaction monitoring( MRM) quantitative analysis was made to establish a determination method for drug concentrations of costunolide( Co) and dehydrocostuslactone( De) in blood samples in the positive ion mode,with diazepam as the internal standard substance,in order to study the pharmacokinetic process of sesquiterpene lactones costunolide and dehydrocostuslactone after the oral administration of Weichang' an pills,and provide an theoretical basis for further studies on the substance basis for the anti-diarrhea effect of Weichang'an pills. In the blood samples,Co and De showed a good linearity within concentration ranges 0. 700 0-769. 7,2. 510-956. 0 μg·L-1,respectively. The results of precision,stability and recovery experiences proved the stability and reliability of the plasma concentration determination method. After the oral administration,the concentrations of Co and De in plasma increased with the increase in dose,with Tmaxbetween 10. 65-12. 98 h,indicating a long time to reach peak plasma concentrations; Cmaxof costunolide and dehydrocostuslactone ranged between 3. 750-5. 450,15. 34-44. 52 μg·L-1,respectively. The in vivo adsorption of Co and De conformed to the one-compartment model,with a longer time to attain the peak plasma concentrations.These results provided an experimental basis for revealing the active substance basis and clinical medication of Weichang'an pills.

关键词(KeyWords): 胃肠安丸;木香烃内酯;去氢木香内酯;药代动力学
Weichang'an pills;costunolide;dehydrocostuslactone;pharmacokinetics

Abstract:

Keywords:

基金项目(Foundation): 天津市应用基础与前沿技术研究计划自然科学基金青年项目(13JCQNJC13000);; 武警后勤学院创新团队项目军队特需药物创制项目(WHTD201304)

作者(Author): 张静泽;王磊;金兆祥;曲卓;陈钰玲;高文远;
ZHANG Jing-ze;WANG Lei;JIN Zhao-xiang;QU Zhuo;CHEN Yu-ling;GAO Wen-yuan;Special Military Drug R&D Center,Logistics University of Chinese People's Armed Police Forces;Tianjin Lerentang Pharmaceutical Factory,Tianjin Zhongxin Pharmaceuticals Group Co. ,Ltd.;School of Pharmaceutical Science and Technology,Tianjin University;

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