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毛细管区带电泳测定人血浆中麦考酚酸浓度

熊祯, 段京莉*, 翟所迪, 赵磊, 徐彭   

  1. 1. 北京大学第三医院 药剂科, 北京 100191
    2. 北京大学第三医院 泌尿外科, 北京 100191
    3. 江西中医学院 药学院, 江西 南昌 330006
    4. 北京大学 治疗药物监测和临床毒理中心, 北京 100191
  • 收稿日期:2009-05-15 修回日期:2009-10-15 出版日期:2009-11-30 发布日期:2009-11-30
  • 通讯作者: 段京莉*

A simple capillary zone electrophoresis method for the determination of mycophenolic acid in human plasma

Zhen Xiong, Jing-Li Duan*, Suo-Di Zhai, Lei Zhao, Peng Xu   

  1. 1. Department of Pharmacy, Peking University Third Hospital, Beijing 100191, China
    2. Department of Urinary Surgery, Peking University Third Hospital, Beijing 100191, China
    3. College of Pharmaceutical Sciences, Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, China
    4. Peking University Therapeutic Drug Monitoring & Clinical Toxicology Center, Beijing 100191, China
  • Received:2009-05-15 Revised:2009-10-15 Online:2009-11-30 Published:2009-11-30
  • Contact: Jing-Li Duan*

摘要: 建立了人血浆中麦考酚酸浓度的毛细管区带电泳测定法。200 µL的血浆样品经400 µL的乙腈沉淀蛋白后, 紧接一段水柱进样, 进样量为: 0.5 psi×10 s。分离采用内径75 µm, 有效长度50 cm的未涂层熔硅弹性石英毛细管柱。通过均匀设计实验, 选定pH为8.60的硼酸缓冲液 (硼酸初始浓度为200 mmol/L) 为背景缓冲液。结果显示, 测定方法的标准曲线在0.625~30.0 µg/mL的范围内, r 平均值大于0.9997; 检测下限为0.200 µg/mL; 日内、日间精密度均小于4.45%。应用本方法和高效液相色谱-串联质谱法, 对14份接受麦考酚酸酯治疗的肾移植术后患者的血样进行分析, 表明本方法准确、精密、经济, 对于麦考酚酸的临床定量极具价值。

关键词: 麦考酚酸, 毛细管区带电泳, 均匀设计

Abstract: Mycophenolic acid (MPA), an immunosuppressive drug, was determined in human plasma by a simple capillary zone electrophoresis (CZE) method. A bare fused-silica capillary with an internal diameter (i.d.) of 75 µm and an effective length of 50 cm was used for the separation. A 200 μL plasma sample was deproteinized with 400 μL acetonitrile, and the supernatant was directly injected into the capillary after a water plug at a pressure of 0.5 psi for 10 s. Boric acid (H3BO3, 200 mmol/L) solution adjusted to a pH of 8.60 with 1 mol/L sodium hydroxide (NaOH) solution was selected as the background electrolyte (BGE) through a uniform design. Calibration curve established on each day was linear over the MPA concentration range of 0.625-30.0 μg/mL in human plasma with the correlation coefficient (r) larger than 0.9997. The limit of detection (LOD) was 0.200 μg/mL. Intra- and inter-day precisions at three concentrations within the calibration range were less than 4.45%. Plasma samples collected from 14 renal transplant recipients treated with the prodrug mycophenolate mofetil (MMF) were analyzed successfully by both the developed CZE technique and a validated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) technique. The mean absolute and relative differences between the concentrations measured by the two methods were -0.17 and -0.20%, respectively. In conclusion, the CZE method described here was validated to be accurate, precise, and economical for the clinical quantification of MPA.

Key words: Mycophenolic acid, Capillary zone electrophoresis, Uniform design

中图分类号: 

Supporting:

Foundation items: Plan of Vitalizing Education Action Geared to the 21st Century (Plan 985) and the 1st Phase Fund of Peking University 985 Project.
*Corresponding author. fax: 86-10-82265740; e-mail: duanjl@bjmu.edu.cn