Stereoselective pharmacokinetics of (R)-(+)- and (S)-(-)-rabeprazole in human using chiral LC-MS/MS after administration of rabeprazole sodium enteric-coated tablet.

Stereoselective pharmacokinetics of (R)-(+)- and (S)-(-)-rabeprazole in human using chiral LC-MS/MS after administration of rabeprazole sodium enteric-coated tablet.
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雷贝拉唑钠肠溶片给药后,使用手性 LC-MS/MS 测定 (R)-( )- 和 (S)-()-雷贝拉唑在人体内的立体选择性药代动力学

DOI:
10.1002/chir.23022
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发表时间:
2018-10
期刊:
影响因子:
2
通讯作者:
Wang Yong-Qing
Wang Yong-Qing
中科院分区:
化学4区
文献类型:
--
作者:
Sun Lu-Ning;Shen Yi-Wen;Ying Yu-Wen;Li Duo;Li Teng-Fei;Zhang Xue-Hui;Zhao Ping;Ding Li;Wang Yong-Qing

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雷帕霉素是一种有效的质子泵抑制剂,用于治疗酸相关疾病。建立了同时测定人血浆中雷贝拉唑对映体浓度的手性LC-MS/MS方法。使用含0.1%铵的乙腈作为蛋白质沉淀剂。分析物在Chiralpak IC柱(4.6 mm × 150 mm,5 μm)上在8分钟内分离。移动的相为10 mM乙酸铵,包括0.2%乙酸-乙腈(35:65,v/v)。采用API 4000型质谱仪检测器,选择m/z为360.1 → 242.2和346.1 → 198.1的多反应监测模式定量雷贝拉唑对映体和内标物。各对映体和内标物(埃索美拉唑)的基质效应不明显,校准曲线在0.500 - 400 ng·mL-1浓度范围内呈线性,批内精密度低于5.4%,批间精密度低于9.9%,准确度在-9.2%至9.3%之间。在样品储存、制备程序和分析过程中未观察到手性转化,证明分析物在本研究中稳定。将该方法应用于中国健康受试者口服10 mg雷贝拉唑钠肠溶片后(R)-(+)-和(S)-(-)-雷贝拉唑的立体选择性药代动力学研究。
Rabeprazole is an effective proton pump inhibitor to treat acid-related diseases. To achieve the simultaneous determination of rabeprazole enantiomers in human plasma, a chiral LC-MS/MS method was developed and validated. Acetonitrile including 0.1% ammonium were used as protein precipitating agent. Analytes were separated within 8 minutes on a Chiralpak IC column (4.6 mm × 150 mm, 5 μm). The mobile phase was 10 mM ammonium acetate including 0.2% acetic acid-acetonitrile (35:65, v/v). An API 4000 mass spectrometer was used as detector for the analysis, and the multiple reactions monitoring transitions of m/z 360.1 → 242.2 and 346.1 → 198.1 were opted for quantifying rabeprazole enantiomers and internal standard. Matrix effects were not apparent for each enantiomer and internal standard (esomeprazole), the calibration curves were linear over the concentration of 0.500 to 400 ng·mL-1 , the intra-run precisions were below 5.4%, the inter-run precisions were below 9.9%, and the accuracy was between -9.2% and 9.3%. There was no chiral inversion observed during sample storage, preparation procedure, and analysis, demonstrating that analytes were stable in this study. This method was applied to the stereoselective pharmacokinetic study of (R)-(+)- and (S)-(-)-rabeprazole after oral administration of 10-mg rabeprazole sodium enteric-coated tablet in healthy Chinese subjects.
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
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