液相色谱-串联质谱法同时测定小鼠血浆中CTN986、芦丁和曲克芦丁的浓度及其在药动学研究中的应用  

Simultaneous quantification of CTN986,rutin and troxerutin in mice plasma by LC-MS /MS: application to a pharmacokinetic study

作　　者：陈娟鹃[1,2] 孟繁华[2] 张杨[2] 郭继芬[2] 王迪敏[2,3] 王松[2,4] 

机构地区：[1]中南大学,长沙410083 [2]军事医学科学院毒物药物研究所,北京100850 [3]沈阳药科大学,沈阳110016 [4]北京化工大学,廊坊065201

出　　处：《国际药学研究杂志》2013年第2期248-253,共6页Journal of International Pharmaceutical Research

基　　金：国家自然科学基金青年基金资助项目(81001468);综合性新药研究开发大平台(2012ZX09301003-001)

摘　　要：目的建立同时测定小鼠血浆中CTN986、芦丁和曲克芦丁浓度的LC-MS/MS法并将其应用于小鼠药代动力学研究。方法血浆样品经固相萃取后,以甲醇-异丙醇-水-甲酸(体积比为36∶8∶56∶0.1)为流动相,通过Discovery C18柱(250 mm×4.6 mm,5μm)分离,采用ESI源以多反应监测(MRM)方式进行正离子检测。用于定量分析的离子反应分别为m/z 743→m/z 303(CTN986),m/z 611→m/z 303(芦丁),m/z 745→m/z 435(曲克芦丁),m/z 727→m/z 287(CTN987,内标)。结果CTN986、芦丁和曲克芦丁的线性范围均为4～800 ng/ml,日内、日间精密度(RSD)均小于14.65%,准确度(RE)在-0.34%～11.75%。应用此法考察了小鼠口服和静注上述3个化合物后的药动学特征,以及P-gp抑制剂维拉帕米对三者药动学行为的影响。结论本方法专属性强、灵敏度高,适用于CTN986、芦丁和曲克芦丁的药代动力学研究。Objective An LC-MS/MS method for the simultaneous determination of CTN986, rutin and troxerntin in mice plasma was developed and validated for the pharmacokinetics study. Methods Plasma samples were prepared by Cls solid-phase ex- traction. Isocratic chromatographic separation was performed on a reversed-phase Discovery C ls column （250 mmx 4. 6 mm, 5 ~Lm）. The mobile phase was methanol-isopropanol- water-formic acid （36： 8： 56： 0. 1, V/V/V/V）. Detection of CTN986, rutin, troxerutin and the internal standard （IS） CTN987 was achieved by ESI-MS/MS in the positive ion mode using m/z 743---~m/z 303, m/z 611-＊m/z 303, m/z 743--,m/z 435 and m/z 727---~m/z 287 transitions, respectively. Results The method was proved to be linear from 4 to 800 ng/ml for CTN986, rutin and troxerntin when 100 ~L1 plasma was analyzed. The lower limit of quantification was 4 ng/ml. The intra- and inter-day precision values were both below 14. 65%, and accuracy ranged from -0. 34% to 11.75% in all quality control sam- ples. The validated method was successfully applied to the investigation of the pharmacokinetic profile of CTN986, rutin and troxerutin in mice. Conclusion The method is proved to be suitable for the pharmacokinetic study of CTN986, rntin and troxerutin.

关 键 词：液相色谱-串联质谱法 CTN986 芦丁 曲克芦丁 P-糖蛋白 药代动力学 

分 类 号：R969[医药卫生—药理学]