超高效液相色谱-质谱联用技术同时检测大鼠血浆中蒿甲醚及其主要代谢产物双氢青蒿素  

Simultaneous Determination of Artemether and Its Major Metabolites Dihydroartimisinin in Rat Plasma Using Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry

作　　者：李春[1,2] 邱玉琴[1] 杨国忠[1,2] 孟凡达[1,2] 张锁慧[1] 高云华[1] 

机构地区：[1]中国科学院理化技术研究所光化学转换和功能材料重点实验室,北京100190 [2]中国科学院大学,北京100049

出　　处：《分析化学》2015年第4期588-593,共6页Chinese Journal of Analytical Chemistry

摘　　要：为了研究蒿甲醚在大鼠体内的药代动力学行为,应用液液萃取-超高效液相色谱-单四极杆-静电场轨道阱串联质谱技术,建立了高灵敏度的大鼠血浆中蒿甲醚及其主要代谢产物双氢青蒿素的分析方法。以青蒿素为内标（Internal standard,I.S.）,在正离子Targeted-MS2检测模式下对蒿甲醚和双氢青蒿素进行定性和定量分析。检测离子对分别为m/z 316.2115/163.1117（蒿甲醚）、m/z 302.1958/163.1117（双氢青蒿素）和m/z 300.1803/209.1536（I.S.）;蒿甲醚和双氢青蒿素在2-200μg/L范围内线性关系良好（R2〉0.9990）;检出限为0.8μg/L;定量限为2.0μg/L;加标回收率分别为93.7%-103.7%和97.4%-104.7%;相对标准偏差均小于9%。本方法快速灵敏,重现性好,可用于蒿甲醚体内药代动力学研究。In order to study the pharmacokinetics of artemether in rats,artemether and its major metabolites dihydroartimisinin in rat plasma were simultaneously determined by an ultra performance liquid chromatography coupled with quadrupole-obitrap mass spectrometric method with high sensitivity. Artemisinin was used as internal standard. Identification and quantification of artemether and dihydroartimisinin were performed with electrospray ionization under a positive Targeted-MS2 monitoring mode. The monitored transitions were m / z316. 2115 /163. 1117（ artemether）,m / z 302. 1958 /163. 1117（ dihydroartimisinin） and m / z 300. 1803 /209. 1536（ artemisinin）. A good linearity was obtained in the range of 2- 200 μg / L（ R^2〉 0. 9990） with a limit of detection of 0. 8 μg / L and a limit of quantification of 2. 0 μg / L for both artemether and dihydroartimisinin. The recoveries of artemether and dihydroartimisinin were 93. 7%- 103. 7% and 97. 4%-104. 7%,respectively. The RSD was less than 9%. The method is rapid,sensitive,reproducible,and can be applied in pharmacokinetic studies of artemether in rats.

关 键 词：蒿甲醚 双氢青蒿素 静电场轨道阱 大鼠血浆 药代动力学 

分 类 号：R285.5[医药卫生—中药学] O657.63[医药卫生—中医学]