| 引用本文: | 乔勇,童焕,郭思维,徐兵,蒋蓉,邓阳,李昕.利福平全血稳定性研究及治疗药物监测的临床采样流程建立[J].中国现代应用药学,2025,42(7):133-140. |
| qiaoyong,TONG Huan,GUO Siwei,XU Bing,JIANG Rong,DENG Yang,LI Xin.Investigation into the stability of rifampicin in whole blood and development of a clinical sampling protocol for therapeutic drug monitoring[J].Chin J Mod Appl Pharm(中国现代应用药学),2025,42(7):133-140. |
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| 利福平全血稳定性研究及治疗药物监测的临床采样流程建立 |
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乔勇, 童焕, 郭思维, 徐兵, 蒋蓉, 邓阳, 李昕
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长沙市第三医院
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| 摘要: |
| 目的 建立HPLC-MS/MS法测定人血浆中利福平浓度,基于全血稳定性结果制定临床采样及送检流程,以期为利福平治疗药物监测及个体化给药方案设计提供参考。方法 血浆样品经乙腈沉淀蛋白,取上清液-水(v/v,1:1)稀释后进样；以0.1%甲酸水-乙腈(v/v,55:45)为流动相；经色谱柱Ultimate AQ-C18(3.0 mm×100 mm,3.0 μm)、预柱SecurityGuardTM Standard C18(2.0 mm×4.0 mm,2.0 μm)分离；流速:0.4 mL?min-1；柱温:45 ℃；质谱采用电喷雾离子源,以多反应监测模式进行定量分析；分别考察利福平全血和血浆样本于不同条件下的稳定性,基于全血稳定性结果制定临床采样及送检流程,并应用于临床治疗药物监测。结果 利福平在0.16~45.00 μg?mL-1范围内线性关系良好(r=0.9998),定量下限为0.16 μg?mL-1,低、中、高浓度的萃取回收率在86.68%~114.26%范围内,日内、日间精密度RSD均小于2.74%；肝素钠采血管的全血样本避光条件下于室温(18~23 ℃)24 h、4 ℃冰箱48 h内稳定,优于同等放置条件下EDTA-K2采血管(4 h、12 h内稳定),血浆质控样品经预处理后于自动进样器(4 ℃)16 h稳定,血浆质控样品于室温(18~23 ℃)4 h、-40 ℃冻存30 d、-40 ℃反复冻融3次均稳定。结论 建立的利福平治疗药物监测方法及临床采样流程能确保利福平的稳定性及检测结果的准确性,为利福平的治疗药物监测标准化与规范化建设提供参考依据。 |
| 关键词: 利福平 治疗药物监测 全血稳定性 临床采样流程 液相色谱-质谱联用 |
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| 基金项目:抗耐药微生物药物湖南省重点实验室(No:2023TP1013)；湖南省自然科学基金面上项目(No:2023JJ30059)；湖南省临床医疗技术创新引导项目(No:2020SK52901) |
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| Investigation into the stability of rifampicin in whole blood and development of a clinical sampling protocol for therapeutic drug monitoring |
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qiaoyong, TONG Huan, GUO Siwei, XU Bing, JIANG Rong, DENG Yang, LI Xin
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The Third Hospital of Changsha
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| Abstract: |
| ABSTRACT: OBJECTIVE An HPLC-MS/MS method was developed to quantify rifampicin levels in human plasma, with clinical samp ling and delivery protocols designed according to whole blood stability findings, to serve as a foundation for Therapeutic Drug Monitoring and personalized drug administration program development. METHODS The plasma samples underwent precipitation with acetonitrile, followed by dilution of the supernatant with water in a volumetric ratio of 1:1. The mobile phase utilized in the chromatographic separation consisted of 0.1% formic acid-acetonitrile in a volumetric ratio of 55:45. The separation was achieved using an Ultimate AQ-C18 column (3.0 mm×100 mm, 3.0 μm) coupled with a pre-column SecurityGuardTM Standard C18 (2.0 mm×4.0 mm, 2.0 μm). The flow rate was set at 0.4 mL?min-1, with a column temperature of 45 ℃. Mass spectrometry analysis was conducted using an electrospray ion source, employing a multi-reaction monitoring mode for quantitative assessment. The study examined the stability of rifampicin in whole blood and plasma samples under various conditions. The findings from the whole blood stability analysis informed the development of clinical sampling and examination protocols, as well as the implementation of therapeutic drug monitoring in clinical practice. RESULTS Rifampicin exhibited a strong linear correlation within the concentration range of 0.16~45.00 μg?mL-1 (r=0.9998), with a lower limit of quantification of 0.16 μg?mL-1. The recovery rates for low, medium, and high concentrations ranged from 86.68% to 114.26%, and the precision RSD for intra-day and inter-day analyses was below 2.74%. Stability studies revealed that whole blood samples containing heparin sodium remained stable at room temperature（18~23 ℃）for 24 hours and in the refrigerator at 4 ℃ for 48 hours under dark conditions, surpassing the stability of EDTA-K2 samples under the same conditions (stable for 4 hours and 12 hours, respectively). The plasma quality control samples demonstrated stability when stored at an automatic injector at 4 ℃ for 16 hours following pretreatment. Additionally, the plasma samples remained stable at room temperature (18~23 ℃) for 4 hours, were frozen at -40 ℃ for a period of 30 days, and underwent three freeze-thaw cycles at -40 ℃. CONCLUSION The validated rifampicin Therapeutic Drug Monitoring method and clinical sampling protocol contribute to the maintenance of rifampicin stability and the precision of analytical outcomes, thereby offering insights for the establishment of standardized practices in Rifampicin Therapeutic Drug Monitoring. |
| Key words: rifampicin therapeutic drug monitoring whole blood stability clinical sampling process HPLC-MS/MS |
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