• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>other >Ultra-performance liquid chromatography tandem mass spectrometry method for the determination of AZ66 a sigma receptor ligand in rat plasma and its application to in vivo pharmacokinetics
【2h】

Ultra-performance liquid chromatography tandem mass spectrometry method for the determination of AZ66 a sigma receptor ligand in rat plasma and its application to in vivo pharmacokinetics

机译：超高效液相色谱串联质谱法测定大鼠血浆中的sigma受体配体AZ66及其在体内药代动力学中的应用

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Methamphetamine abuse continues as a major problem in the USA owing to its powerful psychological addictive properties. AZ66, 3-[4-(4-cyclohexylpiperazine-1-yl)pentyl]-6-fluorobenzo[d]thiazole-2(3H)-one, an optimized sigma receptor ligand, is a promising therapeutic agent against methamphetamine. To study the in vivo pharmacokinetics of this novel sigma receptor ligand in rats, a sensitive ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) method was developed in rat plasma and validated. The developed method requires a small volume of plasma (100 μL) and a simple liquid–liquid extraction. The chromatographic separations were achieved in 3.3 min using an Acquity UPLC BEH Shield RP18 column. The mass spectrophotometric detection was carried out using a Waters Micromass Quattro MicroTM triple-quadrupole system. Multiple reaction monitoring was used for the quantitation with transitions m/z 406→m/z 181 for AZ66 and m/z 448→m/z 285 for aripiprazole. The method was validated over a concentration range of 1–3500 ng/mL and the lower limit of quantitation was determined to be 1 ng/mL. Validation of the assay demonstrated that the developed UPLC/MS/MS method was sensitive, accurate and selective for the determination of AZ66 in rat plasma. The present method has been successfully applied to an i.v. pharmacokinetic study in Sprague–Dawley rats.
机译：甲基苯丙胺滥用由于其强大的心理成瘾性而继续在美国成为主要问题。 AZ66，3- [4-（4-环己基哌嗪-1-基）戊基] -6-氟苯并[d]噻唑-2（3H）-是一种经过优化的sigma受体配体，是一种针对甲基苯丙胺的有前途的治疗剂。为了研究这种新的sigma受体配体在大鼠体内的药代动力学，在大鼠血浆中建立了灵敏的超高效液相色谱/串联质谱（UPLC / MS / MS）方法并进行了验证。开发的方法需要少量血浆（100μL）和简单的液-液萃取。使用Acquity UPLC BEH Shield RP18色谱柱在3.3分钟内完成色谱分离。使用Waters Micromass Quattro MicroTM三重四极杆系统进行质谱检测。多重反应监测用于定量，对于AZ66为m / z 406→m / z 181，对于阿立哌唑为m / z 448→m / z 285。该方法在1–3500 ng / mL的浓度范围内得到验证，定量下限为1 ng / mL。该方法的验证表明，所开发的UPLC / MS / MS方法对大鼠血浆中AZ66的测定灵敏，准确且具有选择性。本方法已成功地应用于i.v. Sprague–Dawley大鼠的药代动力学研究。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号