首都医科大学学报 ›› 2026, Vol. 47 ›› Issue (3): 457-469.doi: 10.3969/j.issn.1006-7795.2026.03.007

• 从分子机制到临床应用:创新药物新突破 • 上一篇    下一篇

血浆中4种抗结核病药物的候选参考方法建立和性能评价

缪文瑄1,2,陈启3,梅升辉1*   

  1. 1. 首都医科大学附属北京天坛医院药学部，北京  100070；2. 首都医科大学燕京医学院检验医学系，北京 101300；3. 浙江树人学院树兰国际医学院，杭州  310000
  • 收稿日期:2026-02-02 修回日期:2026-04-15 出版日期:2026-06-21 发布日期:2026-06-26
  • 通讯作者: 梅升辉 E-mail:meishenghui1983@126.com
  • 基金资助:
    北京市医管局培育计划项目（PX2024020），国家重点研发计划项目（2020YFC2008306）。

Establishment and performance evaluation of a candidate reference method for 4 anti-tuberculosis drugs in human plasma

Miao Wenxuan1,2 ,  Chen Qi3 ,  Mei Shenghui1*   

  1. 1. Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, Beijing 100070,  China; 2. Department of Laboratory Medicine, Yanjing Medical College, Capital Medical University， Beijing 101300,   China; 3. Shulan International Medical College of Zhejiang Shuren University, Hangzhou 310000, China
  • Received:2026-02-02 Revised:2026-04-15 Online:2026-06-21 Published:2026-06-26
  • Supported by:
    This study was supported by Beijing Municipal Hospital Administration Cultivation Program (PX2024020) and National Key Research and Development Program (2020YFC2008306).

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摘要： 目的  建立可准确、灵敏测定人血浆中利福平、异烟肼、吡嗪酰胺和乙胺丁醇4种一线抗结核药物的方法，为临床精准诊疗提供技术支撑。方法  采用超高效液相色谱-串联质谱技术，以利福平-d8、异烟肼-d4、乙胺丁醇-d4和吡嗪酰胺-d3为内标，乙腈为提取液；血液样品经离心后取上清液直接进样分析。流动相为0.1%（体积分数）甲酸水溶液/甲醇，流速0.3 mL/min，柱温40 ℃，进样体积1 μL。依据《中华人民共和国药典》通则9012完成特异度、线性、精密度、准确度、基质效应及稳定性等方法学验证。结果  4种药物在各自浓度范围内均呈良好线性关系，校正曲线决定系数（r2）均大于0.995；批内回收率为94.4%~108.2%，精密度小于6.34%；批间回收率为92.4%~104.8%，精密度小于4.44%，各项指标均符合方法学验证要求。结论  本研究建立的人血浆中4种一线抗结核药物浓度测定方法，具有准确、简便、灵敏、线性范围宽等优点，可为抗结核治疗药物监测及个体化给药方案制定提供可靠的技术支持。

关键词: 抗结核药物, 治疗药物监测, 利福平, 异烟肼, 吡嗪酰胺, 乙胺丁醇, 超高效液相色谱-串联质谱

Abstract: Objective  To establish a candidate reference method for the simultaneous, accurate and sensitive determination of four first-line anti-tuberculosis drugs (rifampicin, isoniazid, pyrazinamide and ethambutol) in human plasma, and to provide technical support for individualized and precise clinical diagnosis and treatment. Methods  An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed. Rifampicin-d8, isoniazid-d4, ethambutol-d4 and pyrazinamide-d3 were used as internal standards, and acetonitrile was selected as the extraction solvent for the quantitative determination of the four drugs in human plasma. The blood samples were centrifuged, and the supernatant was directly injected for analysis. The mobile phase was composed of 0.1% formic acid aqueous solution (v/v) (A) and methanol (B). The flow rate was set as 0.3 mL/min, the column temperature was set at 40℃ and the injection volume was 1 μL. Methodological validation was performed according to General Chapter 9012 of the Chinese Pharmacopoeia, including specificity, linearity, precision, accuracy, matrix effect and stability. Results  All four drugs showed good linearity in their respective concentration ranges, with all the correlation coefficients (r2) of the calibration curves greater than 0.995. The intra-batch recoveries were in the range of 94.4% to 108.2% with the relative standard deviations (RSD) less than 6.34%, and the inter-batch recoveries were 92.4% to 104.8% with the RSD less than 4.44%. All the validation parameters met the requirements of methodological verification. Conclusion  The established UPLC-MS/MS method for the determination of four first-line anti-tuberculosis drugs in human plasma is accurate, rapid, simple, and highly sensitive, with a wide linear range. It provides a reliable technical basis for therapeutic drug monitoring (TDM) and individualized dosing regimens for anti-tuberculosis treatment.

Key words: anti-tuberculosis drugs, therapeutic drug monitoring, rifampicin, isoniazid, pyrazinamide, ethambutol, ultra performance liquid chromatography-tandem mass spectrometry

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