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LC-MS-MS法测定人血浆中克拉霉素含量及其在药物动力学中的应用

张向荣, 陈笑燕, 李小燕, 钟大放*   

  1. 沈阳药科大学药物代谢与药物动力学实验室, 沈阳 110016
  • 收稿日期:2004-04-20 修回日期:2004-08-10 出版日期:2004-09-15 发布日期:2004-09-15
  • 通讯作者: 钟大放*

Determination of Clarithromycin in Human Plasma by Liquid Chromatography-Tandem Mass Spectrometry: Validation and Application in Clinical Pharmacokinetic Study

ZHANG Xiang-rong, CHEN Xiao-yan, LI Xiao-yan, ZHONG Da-fang*   

  1. Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, Shenyang 110016, China
  • Received:2004-04-20 Revised:2004-08-10 Online:2004-09-15 Published:2004-09-15
  • Contact: ZHONG Da-fang*

摘要: 目的 建立测定人血浆中克拉霉素的液相色谱-串联质谱法, 研究市售片剂在人体的药物动力学特点.方法 以罗红霉素为内标, 取血浆样品0.2 mL经液-液提取后, 以甲醇--甲酸(80:20:0.5)为流动相, C18柱分离, 采用电喷雾离子源三重四极杆串联质谱, 正离子方式检测, 扫描方式为选择反应监测(SRM). 结果 克拉霉素线性范围为10.0-5000ng·mL-1, 日内、日间精密度(RSD)均小于3.3%, 准确度(RE)±0.7%以内.应用此法研究18名健康受试者单剂量口服250 mg克拉霉素市售片的药动学参数TmaxCmaxT1/2AUC0-24h值分别为(3.1±2.7)h(8 750±4734)ng·mL-1(5.3±2.2) h(5932±249)ng·h·mL-1. 结论 该法用于人体药物动力学的研究专属、快速、灵敏.

关键词: 克拉霉素, 克拉霉素, 克拉霉素, 液相色谱质谱联用法, 液相色谱质谱联用法, 液相色谱质谱联用法, 药物动力学, 药物动力学, 药物动力学

Abstract:

Aim To develop a liquid chromatographic-tandem mass spectrometric (LC-MS-MS) method to determine clarithromycin in human plasma. Methods The analyte and internal standard roxithromycin were extracted from plasma samples by n-nexane-dichloromethane-isopropanol (300:150:15, V/V/V) and chromatographed on a C18 column. The mobile phase consisted of methanol-water-formic acid (80:20:1, V/V/V). Detection was performed on a triple quadrupole tandem mass spectrometer via electrospray ionization source (ESI) in the positive mode. Results The method had a lower (limit) of quantification of 10.0 ng·mL-1 when 0.2 mL plasma was used. The linear calibration curves were obtained in the concentration range of 10.0-5000 ng·mL-1. The intra- and inter-run precisions were lower than 3.3% in terms of relative standard deviation (RSD), and the accuracy ranged ±0.7% in terms of relative error (RE). Tmax, Cmax, T1/2 and AUC0-24h values were found to be (3.1±2.7)h, (8750±4734)ng·mL-1, (5.3±2.2) h, and (5 932±2 449)ng·mL-1, respectively, after a single oral dose of 250 mg clarithromycin tablet to 18 volunteers. Conclusion This validated method was successful in the evaluation of pharmacokinetic profiles of clarithromycin tablets administered to 18 healthy male volunteers.

Key words: clarithromycin, clarithromycin, LC-MS-MS, LC-MS-MS, pharmacokinetics, pharmacokinetics

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Supporting: *Corresponding author. Tel.: 86-24-23902539