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LC-MS法测定人血浆中尼美舒利含量及其生物等效性研究

杨雯雯, 房丽娜, 郝桂彤, 刘丽霞, 杨红英, 孙立新*   

  1. 1. 沈阳药科大学 药学院, 辽宁 沈阳 110016;
    2. 天津怀仁制药有限公司, 天津 300193
  • 收稿日期:2010-05-28 修回日期:2010-08-10 出版日期:2010-09-20 发布日期:2010-09-20
  • 通讯作者: 孙立新*

A simple and robust HPLC-MS method for the quantitative determination of nimesulide in human plasma and its application to bioequivalence study in Chinese volunteers

Wen-Wen Yang, Li-Na Fang, Gui-Tong Hao, Li-Xia Liu, Hong-Ying Yang, Li-Xin Sun*   

  1. 1. Department of Pharmaceutical Analysis, Shenyang Pharmaceutical University, Shenyang 110016, China
    2. Tianjin Huairen Pharmaceutical Company Limited, Tianjin 300193, China
  • Received:2010-05-28 Revised:2010-08-10 Online:2010-09-20 Published:2010-09-20
  • Contact: Li-Xin Sun*

摘要: 建立和确证了适用于测定人血浆中尼美舒利含量的液相色谱-质谱(LC-MS)方法, 并对尼美舒利参比和受试制剂进行生物等效性评价。人血浆样品(100 µL)采用液液萃取法提取, 内标为氢氯噻嗪。采用C18柱, 以甲醇-水(86:14, v/v)为流动相, 选择离子监测负离子模式检测, 尼美舒利m/z为307.00, 内标氢氯噻嗪m/z为295.90。分析时间4.2分钟。尼美舒利在20.0-7000.0 ng/mL浓度范围内线性关系良好, 定量下限20.0 ng/mL。内源性物质不干扰尼美舒利和内标的检测, 无基质效应。尼美舒利和内标氢氯噻嗪的平均提取回收率均大于84.4%。所建立的方法已成功应用于尼美舒利生物等效性研究。

关键词: 尼美舒利, HPLC-MS, 定量, 人血浆, 生物等效性

Abstract: A rapid and sensitive high performance liquid chromatography-mass spectrometry (HPLC-MS) method for the quantification of nimesulide in human plasma was developed and validated. Sample aliquots of 100 µL were extracted by one-step liquid-liquid extraction after addition of hydrochlorothiazide as the internal standard (IS). Analytes were separated on a reverse phase C18 column using methanol-water (84:16, v/v) as the mobile phase and detected by a single quadrupole mass spectrometer in selected ion monitoring (SIM) negative mode. Monitored m/z values for nimesulide and IS were 307.00 and 295.90, respectively. The overall run time was 4.2 min. Validation experiments demonstrated good precision and accuracy over a wide concentration range of 20.0-7000 ng/mL with a lower limit of quantification (LLOQ) at 20.0 ng/mL. No interference by endogenous substances or matrix effect was observed. Average extraction recoveries for nimesulide and IS were all greater than 84.4%. The assay was successfully applied to a bioequivalence study of nimesulide dispersible tablets in Chinese male volunteers after oral administration.

Key words: Nimesulide, HPLC-MS, Quantification, Human plasma, Bioequivalence

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Supporting: *Corresponding author. Tel.: 86-24-23986365; fax: 86-24-23986259