欢迎访问《中国临床药理学与治疗学》杂志官方网站,今天是 分享到:

中国临床药理学与治疗学 ›› 2008, Vol. 13 ›› Issue (4): 406-411.

• 基础研究 • 上一篇    下一篇

LC-APCI-MS/MS法研究维氨酯在大鼠体内的排泄

曹玲1,2, 郑枫1, 刘文英1, 马鹏程3, 程宣1, 孙棣1   

  1. 1中国药科大学药学院药物分析教研室,南京210009,江苏;
    2江苏省药品检验所,南京210008,江苏;
    3中国协和大学中国医学科学院皮肤病研究所,南京210042,江苏
  • 收稿日期:2008-02-24 修回日期:2008-03-25 出版日期:2008-04-26 发布日期:2020-10-12
  • 通讯作者: 刘文英,女,博士生导师,研究方向:药物分析。Tel:025-83271251 E-mail:lwcpu@126.com;马鹏程,男,研究员,研究方向:皮肤病治疗学。Tel:025-85478929 E-mail:mpc815@163.com
  • 作者简介:曹玲,女,副主任药师,研究方向:药物分析。Tel:025-86632807 E-mail:clidc@sina.com

Study on the excretion of viaminate in rats by LC-APCI-MS、MS

CAO Ling1,2, ZHENG Feng1, LIU Wen-ying1, MA Peng-cheng3, CHENG Xuan1, SUN Di1   

  1. 1 Department of Pharmaceutical Analysis, China Pharmaceutical University, Nanjing 210009, Jiangsu, China;
    2 Jiangsu Institute for Drug Control, Nanjing 210008, Jiangsu, China;
    3 Institute of Dermatology, CAMS and PUMC, Nanjing 210042, Jiangsu, China
  • Received:2008-02-24 Revised:2008-03-25 Online:2008-04-26 Published:2020-10-12

摘要: 目的: 建立LC-APCI-MS/MS法测定大鼠胆汁、尿液和粪便中维氨酯的浓度,对该药在大鼠体内的排泄规律进行研究,为临床试验提供依据。方法: 生物样本经处理后,采用Agilent TC C18色谱柱,甲醇-水-甲酸(93∶7∶0.1)为流动相,辛伐他汀为内标,在三重四极杆串联质谱仪上,采用大气压化学离子化(APCI)、正离子方式选择性离子监测模式,维氨酯和内标的检测离子分别为m/z448283和m/z419285,分别测定尿液、胆汁和粪便中原型物的含量。结果: 胆汁、尿样、粪便中维氨酯的回收率均大于89%,日间和日内的变异系数均小于10%。胆汁和尿液中维氨酯在0.0808~40.4ng/mL浓度范围内线性关系良好(r=0.9972和0.9949),粪便中维氨酯在0.2525~101ng/mL浓度范围内线性关系良好(r=0.9990),维氨酯的定量下限为0.2pg,方法符合生物样品分析要求。维氨酯在粪便中72h内、在尿液中96h内、在胆汁中24h内原型药的平均累积排泄量分别为12.9%、0.003%、0.0001%。结论: 该方法灵敏度高,专属性强,样品前处理简便,分析速度快,可满足大鼠排泄研究中药物浓度测定的要求,大鼠灌胃给药(5mg/kg)后维氨酯从尿液和胆汁中排泄的原型药物很少。

关键词: 维氨酯, 液相色谱-大气压化学离子化-质谱联用法, 排泄

Abstract: AIM: To establish a highly sensitive, rapid and selective liquid chromatography-tandem mass spectrometry (LC-MS MS) method to determinate the viaminate in bile, urine and feces sample of rats .And to study the excretion of viaminate in rats in order to provide a guidance for the clinical trial .METHODS: The concentration of viaminate was determinated on an Aglilent TC C18 column and the mobile phase consisted of methanol-water and formic acid (93 ∶7 ∶0 .1, V/V/V) using simvastatin as internal standard .The de-tection was performed on a trip-quadrupole tandem mass spectrometer by selected ion monitoring (SRM) scan mode via atmospheric pressure chemical ionization (APCI) .The detected ions were m z 448 283 (viami-nate) and m z 419 285(internal standard) respective-ly.The accumulative excretion amount of viaminate was calculated in the urine, feces and bile, respectively.RESULTS: The extraction recoveries of viaminate in bile, urine and feces were more than 89 %.The RSD of intra-run and inter-run precisions were all less than 10 %.The calibration curves were linear over the con-centration ranges of 0 .0808 -40 .4 ng mL(r =0 .9972 and 0 .9949) for the viaminate in bile and urine .The calibration curve was linear over the concentration ranges of 0 .505 -50 .5 ng mL (r =0 .9990) for the viaminate in feces, The limit of quantitation of method for viaminate was 0 .2 pg .12 .9 %viaminate was found from feces in 72 hours, 0 .003 %was found from urine in 96 hours and 0 .0001 %was detected from bile in 24 hours.CONCLUSION: The method is proved to be accurate, sensitive, selective and convenient .It has successfully been applied to study the excretion of vi-aminate in rats .The amount of viaminate recovered from bile and urine after orally administrated to rat was very low .

Key words: viaminate, liquid chromatography-at-mospheric pressure chemical ionization-tandem mass spectrometry, excretion

中图分类号: