中国药物警戒 ›› 2025, Vol. 22 ›› Issue (4): 386-390.
DOI: 10.19803/j.1672-8629.20240850

• 液相色谱质谱联用法在药物临床评价中的应用研究专栏 • 上一篇    下一篇

超高效液相色谱质谱联用法测定人全血中他克莫司含量不确定度评定

王佳庆1, 汪祺2,△, 刘彤彤3, 张冬婕3, 宁霄4,*   

  1. 1首都医科大学附属北京天坛医院临床试验中心,北京,100050;
    2中国食品药品检定研究院中药民族药检定所,北京 100050;
    3首都医科大学附属北京天坛医院药学部,北京 100050;
    4中国食品药品检定研究院食品化妆品检定所,北京 100050
  • 收稿日期:2024-11-01 发布日期:2025-04-17
  • 通讯作者: *宁霄,女,主任药师,分析化学。E-mail: nx200730079@163.com
  • 作者简介:王佳庆,女,副主任药师,临床试验与药物分析。△为并列第一作者。
  • 基金资助:
    国家重点研发计划（2021YFC2401100）

Uncertainty Evaluation for the Determination of Tacrolimus Content in Human Whole Blood by UPLC-MS/MS Method

WANG Jiaqing1, WANG Qi2,△, LIU Tongtong3, ZHANG Dongjie3, NING Xiao*   

  1. 1Clinical Trial Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China;
    2Institute for Control of Chinese Traditional Medicine and EthnicMedicine, National Institutes for Food and Drug Control, Beijing 100050, China;
    3Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, China;
    4Institute for Food and Cosmetics Testing, National Institutes for Food and Drug Control, Beijing 100050, China
  • Received:2024-11-01 Published:2025-04-17

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摘要： 目的 将不确定度评价方法应用于免疫抑制剂试剂盒的超高效液相色谱-串联质谱联用（UPLC-MS/MS）法检测,建立试剂盒质量评价体系,提高治疗药物监测（TDM）结果的可靠性。方法 采用免疫抑制剂试剂盒进行样品制备,UPLC-MS/MS法进行定量测定人全血中他克莫司（TAC）含量,系统评估测量过程中的不确定度来源,包括重复性、工作液配制和样品制备、仪器允差、标准曲线拟合等,采用A类和B类评定方法对各不确定度分量进行量化评估并合成。结果 通过重复性试验（n=3）评价得到的相对标准测量不确定度ur（1,L）=0.012 8,ur（1,H）=0.012 4;通过B类评定得到的生物样本配制过程相对标准测量不确定度ur（2,L）=0.015,ur（2,H）=0.015;仪器量化引入的相对标准测量不确定度为0.008 2;标准曲线拟合引入的相对标准测量不确定度ur（5,L）=0.008 3,ur（5,H）=0.001 91。经合成后,人全血中TAC低浓度（3.54 mg·L-1）和高浓度（14.89 mg·L-1）样品的合并相对标准测量不确定度分别为0.025 1和0.023 5,扩展不确定度（k=2,P=95%）分别为0.177 8 mg·L-1和0.7 mg·L-1。结论 本研究探索建立不确定度评价方法应用于免疫抑制剂试剂盒的系统评价标准,可有效识别测量过程中的关键误差源,为试剂盒的改进和优化提供参考。

关键词: 他克莫司, 超高效液相质谱联用, 含量测定, 不确定度, 全血

Abstract: Objective To evaluate the uncertainty of human whole blood tacrolimus (TAC) by ultra-performance liquid chromatography-mass spectrometry coupled with immunosuppressant kits. Methods The source of uncertainty in the concentration of TAC in human whole blood was analyzed and synthesized by UPLC-MS/MS. Results The extended uncertainty of a low concentration (3.54 mg·L-1) and a high concentration (14.89 mg·L-1) of TAC in human whole blood was 0.177 8 mg·L-1 and 0.7 mg·L-1, respectively (P=95%, k=2). Conclusion In this study, we have explored the establishment of a systematic evaluation standard for applications of uncertainty evaluation methods to immunosuppre-ssant kits,which can effectively identify the key error sources in the measurement process and provide a reference for the improvement and optimization of the kits.

Key words: Tacrolimus, UPLC-MS/MS, Content Determination, Uncertainty Evaluation, Whole Blood

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