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HPLC-MS/MS法研究奥克梯隆型皂苷元在比格犬血浆中的药代动力学特征

Pharmacokinetic Study of Ocotillol in Beagle Dogs by HPLC-MS/MS
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摘要 目的建立测定比格犬血浆中奥克梯隆型皂苷元奥克梯隆浓度的高效液相色谱-串联质谱(HPLC-MS/MS)检测方法,研究其在比格犬体内的药代动力学特征。方法血浆样品采用甲醇沉淀蛋白法进行提取,通过HPLC-MS/MS分析测定单剂量灌胃给予奥克梯隆后比格犬血浆样品中的药物浓度,获得药-时曲线并计算药代动力学参数。结果奥克梯隆在10-5 000 ng·mL^-1范围内线性关系良好(r>0.998),质控样品的日内和日间精密度(RSD)均小于11.21%,提取回收率均高于82.15%;比格犬灌胃给药15 mg·kg^-1奥克梯隆后,平均血药浓度-时间曲线出现双峰现象,奥克梯隆在比格犬体内的达峰时间(Tmax)为(2.33±0.52)h,峰浓度(Cmax)为(3 486.70±494.24)ng·mL^-1,t1/2为(3.10±0.41)h,血浆中药时曲线下面积(AUC0-t)为(26 491.33±5 394.86)h·ng·mL^-1。结论奥克梯隆口服后达峰较快,消除缓慢,滞留时间较长,体内吸收较少,且该化合物在体内吸收代谢可能存在肝肠循环。 Objective To develop a specific and sensitive high performance liquid chromatography-tandem massspectrometric(HPLC-MS/MS) method for the quantitative analysis of ocotillol in beagle dog plasma, andinvestigate the pharmacokinetic characteristics of ocotillol in beagle dogs after oral administration. Methods Ocotillolwas extracted from plasma by protein precipitation. The concentration of ocotillol in plasma was determined by HPLC-MS/MS and the plasma concentration-time curve and main pharmacokinetic parameters were calculated after a singleoral administration of ocotillol at 15 mg·kg^-1 to beagle dogs. Results Excellent linearity was found between 10-5 000ng·mL^-1 with the correlation coefficient over 0.998. Intra-and inter-day precision values(RSDs) of QC sampleswere both below 11.21% and the extraction recoveries of ocotillol from plasma were higher than 82.15%. Doublepeaks were observed in the mean plasma concentration versus time profile of ocotillol after oral intake. The mainpharmacokinetic parameters of ocotillol were as follows:the mean maximum plasma concentration(Cmax) of ocotillolwas(3 486.70±494.24) ng·mL^-1occurring at(2.33±0.52) h post dose,the mean elimination half-time(t1/2) was(3.10±0.41) h,and the mean area under the plasma concentration versus time curve(AUC0-t) was(2 6491.33±5394.86) h·ng·mL^-1. Conclusion The results indicated that ocotillol was rapidly absorbed and slowly eliminatedfrom circulatory blood system,with low plasma exposure. Meanwhile,double peaks might be relevant to hepato-enteric circulation.
作者 燕晓晶 王佳 杜光光 刘永娥 林迎伟 耿聪 YAN Xiaojing;WANG Jia;DU Guangguang;LIU Yong'e;LIN Yingwei;GENG Gong(The Second Affiliated Hospital of Dalian Medical University,Dalian 116023 Liaoning,China;College of Pharmacy,Jilin University,Changchun 130021 Jilin,China)
出处 《中药新药与临床药理》 CAS CSCD 北大核心 2019年第1期66-71,共6页 Traditional Chinese Drug Research & Clinical Pharmacology
基金 国家自然科学基金(31700293) 大连医科大学附属第二医院博士科研启动基金项目 大连医科大学附属第二医院青年后备人才培养计划项目.
关键词 高效液相色谱-串联质谱 人参皂苷 奥克梯隆型皂苷元 药代动力学 比格犬血浆 HPLC-MS/MS ginsenoside ocotillol pharmacokinetic beagle dog plasma
作者简介 燕晓晶,女,硕士研究生,研究方向:药物代谢与药代动力学研究。Email:cosyyxj@163.com;通信作者:耿聪,女,博士,主管技师,研究方向:药物代谢与药代动力学研究。Email:gc1224@163.com。
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