首页> 外文OA文献 >Stereoselective method to quantify bupropion and its three major metabolites, hydroxybupropion, erythro-dihydrobupropion, and threo-dihydrobupropion using HPLC-MS/MS
【2h】

Stereoselective method to quantify bupropion and its three major metabolites, hydroxybupropion, erythro-dihydrobupropion, and threo-dihydrobupropion using HPLC-MS/MS

机译:使用HPLC-MS / MS的立体选择性方法定量安非他酮及其三种主要代谢物羟基安非他酮,赤二氢安非他酮和苏二氢安非他酮

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。

摘要

Bupropion metabolites formed via oxidation and reduction exhibit pharmacological activity, but little is known regarding their stereoselective disposition. A novel stereoselective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to separate and quantify enantiomers of bupropion, 4-hydroxybupropion, and erythro- and threo-dihydrobupropion. Liquid-liquid extraction was implemented to extract all analytes from 50 μL human plasma. Acetaminophen (APAP) was used as an internal standard. The analytes were separated on a Lux 3 μ Cellulose-3 250×4.6 mm column by methanol: acetonitrile: ammonium bicarbonate: ammonium hydroxide gradient elution and monitored using an ABSciex 5500 QTRAP triple-quadrupole mass spectrometer equipped with electrospray ionization probe in positive mode. Extraction efficiency for all analytes was ≥70%. The stability at a single non-extracted concentration for over 48 h at ambient temperature resulted in less than 9.8% variability for all analytes. The limit of quantification (LOQ) for enantiomers of bupropion and 4-hydroxybupropion was 0.3 ng/mL, while the LOQ for enantiomers of erythro- and threo-hydrobupropion was 0.15 ng/mL. The intra-day precision and accuracy estimates for enantiomers of bupropion and its metabolites ranged from 3.4% to 15.4% and from 80.6% to 97.8%, respectively, while the inter-day precision and accuracy ranged from 6.1% to 19.9% and from 88.5% to 99.9%, respectively. The current method was successfully implemented to determine the stereoselective pharmacokinetics of bupropion and its metabolites in 3 healthy volunteers administered a single 100mg oral dose of racemic bupropion. This novel, accurate, and precise HPLC-MS/MS method should enhance further research into bupropion stereoselective metabolism and drug interactions.
机译:通过氧化和还原形成的安非他酮代谢物具有药理活性,但对其立体选择性配置知之甚少。开发了一种新颖的立体选择性液相色谱-串联质谱(LC-MS / MS)方法,以分离和定量安非他酮,4-羟基安非他酮以及赤-和苏-二氢安非他酮的对映体。实施了液-液萃取以从50μL人血浆中萃取所有分析物。对乙酰氨基酚(APAP)用作内标。使用甲醇:乙腈:碳酸氢铵:氢氧化铵梯度洗脱液在Lux 3μCellulose-3 250×4.6 mm色谱柱上分离分析物,并使用配备电喷雾电离探针的ABSciex 5500 QTRAP三重四极杆质谱仪以正模式进行监测。所有分析物的提取效率均≥70%。在环境温度下单一非提取浓度下超过48小时的稳定性导致所有分析物的变异性均小于9.8%。安非他酮和4-羟基安非他酮对映体的定量限(LOQ)为0.3 ng / mL,而赤-和苏-氢安非他酮对映体的定量限为0.15 ng / mL。安非他酮及其代谢物的对映异构体的日内精确度和准确度估计分别为3.4%至15.4%和80.6%至97.8%,而日间精确度和准确度范围为6.1%至19.9%和88.5之间。 %到99.9%。成功地实施了当前方法,以测定单次口服100mg消旋安非他酮的3名健康志愿者中安非他酮及其代谢产物的立体选择性药代动力学。这种新颖,准确和精确的HPLC-MS / MS方法应加强对安非他酮立体选择性代谢和药物相互作用的进一步研究。

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