HPLC-MS法测定大鼠血浆中银杏萜内酯的浓度及药代动力学研究  

Concentration determination and pharmacokinetic study of ginkolieds by HPLC-MS in rat plasma

作　　者：佟若菲[1,2] 张囡[2] 李维超[2] 房志仲[3] TONG Ruo-fe ZHANG Nan LI Wei-chao FANG Zhi-zhong(Graduate School, Tianjin Medical University, Tianjin 300070,China Pharmacy Department of Pharmacy, Tianjin Children′s Hospital,Tianjin 300074,China College of Pharmacy,Tianjin Medical University,Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics （Theranostics）,Tianjin 300070,China)

机构地区：[1]天津医科大学研究生院,天津300070 [2]天津市儿童医院药剂科,天津300074 [3]天津医科大学药学院天津市临床药物关键技术重点实验室,天津300070

出　　处：《天津医科大学学报》2017年第4期372-376,共5页Journal of Tianjin Medical University

摘　　要：目的:建立HPLC-MS法同时测定大鼠血浆中银杏内酯A(GA)、银杏内酯B(GB)、银杏内酯C(GC)浓度的方法,经系统方法学验证后,应用于大鼠的药代动力学研究。方法:以酮洛芬为内标,以甲醇-10 mmol/L乙酸铵水溶液为流动相,血浆样品中的GA、GB、GC和内标经ZORBAX SB-C18(250 mm×4.6 mm,5μm)色谱柱分离后,采用电喷雾离子源(ESI),负离子一级全扫描模式检测。将建立的方法应用于大鼠静脉注射舒血宁的药代动力学研究。药动学参数由DAS2.0统计软件进行计算。结果:GA、GB和GC均在50~5 000 ng/mL范围内线性关系良好,批内和批间精密度和准确度结果显示,批内、批间变异均小于10%,相对误差分别为-1.0%^-3.0%、-1.2%^-1.5%和-2.9%^-3.2%,方法学考察均符合要求。结论:建立的HPLC-MS法灵敏度高、专属性强,适用于银杏叶提取物制剂中所含银杏萜内酯药动学研究。Objective： To establish HPLC-MS method for simultaneous concentration determination of ginkolides（GA） , ginkolides B （GB）, and ginkolides C （GC） in rat plasma, and to apply it to the pharmacokinetic study in rats. Methods： Ketone ibuprofen was used as internal standard, ammonium acetate in methanol - 10 mmol/L aqueous solution was used as mobile phase, the plasma samples of GA, GB, GC, and internal standard by were divided the ZORBAX SB - C18 （250 mm × 4.6 mm, 5 microns） chromatographic column separation, and by using electrospray ion source （ESI）, negative ion level of full scan mode was detected. The method was used in pharmacokinetic study of shu xuening with intravenous administration in rat. Pharmacokinetic parameters were calculated by DAS2.0 statistical software. Results： GA, GB and GC were in 50 ～ 5000 ng/mL in linear range , and batch variations were less than 10%, the relative errors were -1.0% ～ -3.0%, -1.2% ～ -1.5% and -2.9% ～ -3.2%, respectively. And the methodology met the requirements. Conclusion： The established HPLC-MS method has high sensitivity, strong specificity, and may be suitable for the pharmacokinetic study of the ginkgo biloba extract.

关 键 词：HPLC-MS 银杏内酯 药代动力学 大鼠 

分 类 号：R9[医药卫生—药学]