A chiral LC-MS/MS method for the enantioselective determination of R-(+)- and S-(-)-pantoprazole in human plasma and its application to a pharmacokinetic study of S-(-)-pantoprazole sodium injection
A chiral LC-MS/MS method for the enantioselective determination of R-(+)- and S-(-)-pantoprazole in human plasma and its application to a pharmacokinetic study of S-(-)-pantoprazole sodium injection
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手性LC-MS/MS方法对人血浆中R-(-)-和S-(-)-泮托拉唑对映体选择性测定及其在S-(-)-泮托拉唑钠注射液药动学研究中的应用
DOI：
10.1002/bmc.3980
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发表时间：
2017
影响因子：
1.8
通讯作者：
Wang Yongqing
中科院分区：
文献类型：
--
作者：
Jiao Huiwen;Li Yueqi;Sun Luning;Zhang Hongwen;Yu Liyuan;Yu Lei;Yuan Ziqingyun;Xie Lijun;Chen Juan;Wang Yongqing
泮托拉唑是一种质子泵抑制剂，临床上用于治疗消化性疾病。建立并验证了同时测定人血浆中泮托拉唑对映体的对映选择性LC - MS/MS方法。用乙腈从血浆中提取泮托拉唑对映体和内标物。手性分离在Chiralpak IE色谱柱上进行，流动相为含0.1%乙酸-乙腈（28:7 2,v/v）的10 mm铵乙酸溶液。质谱分析采用API 4000质谱仪。采用m/z384.1→200.1和390.1→206.0的多重反应监测过渡分别定量泮托拉唑对映体和内标。各对映体均无明显基质效应，在5.00 ~ 10,000 ng/mL范围内呈线性关系，日内、日间精密度均在10.0%以下，准确度在-5.6% ~ 0.6%范围内。本方法应用于s‐（-）‐泮托拉唑钠静脉注射后人体立体选择性药代动力学研究。在样品储存、制备和分析过程中均未观察到手性反转。而人血浆中检测到的er‐（+）‐泮托拉唑浓度略高，这表明在某些受试者中，t‐（-）‐泮托拉唑可能转化为toR‐（+）‐泮托拉唑。
Pantoprazole, a proton pump inhibitor, is clinically used for the treatment of peptic diseases. An enantioselective LC‐MS/MS method was developed and validated for the simultaneous determination of pantoprazole enantiomers in human plasma. Pantoprazole enantiomers and the internal standard were extracted from plasma using acetonitrile. Chiral separation was carried on a Chiralpak IE column using the mobile phase consisted of 10 mmammonium acetate solution containing 0.1% acetic acid–acetonitrile (28 : 72,v/v). MS analysis was performed on an API 4000 mass spectrometer. Multiple reactions monitoring transitions ofm/z384.1→200.1 and 390.1→206.0 were used to quantify pantoprazole enantiomers and internal standard, respectively. For each enantiomer, no apparent matrix effect was found, the calibration curve was linear over 5.00–10,000 ng/mL, the intra‐ and inter‐day precisions were below 10.0%, and the accuracy was within the range of –5.6% to 0.6%. This method was applied to the stereoselective pharmacokinetic studies in human after intravenous administration ofS‐(–)‐pantoprazole sodium injections. No chiral inversion was observed during sample storage, preparation procedure and analysis. WhileR‐(+)‐pantoprazole was detected in human plasma with a slightly high concentration, which implied thatS‐(–)‐pantoprazole may convert toR‐(+)‐pantoprazole in some subjects.