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Abstract：
Therapeutic drug monitoring (TDM) uses drug concentrations, primarily from plasma, to optimize drug dosing. Optimisation of drug dosing may improve treatment outcomes, reduce toxicity and reduce the risk of acquired drug resistance. The aim of this narrative review is to outline and discuss the challenges of developing multi-analyte assays for anti-tuberculosis (TB) drugs using liquid chromatography-tandem mass spectrometry (LC-MS/MS) by reviewing the existing literature in the field. Compared to other analytical methods, LC-MS/MS offers higher sensitivity and selectivity while requiring relatively low sample volumes. Additionally, multi-analyte assays are easier to perform since adequate separation and short run times are possible even when non-selective sample preparation techniques are used. However, challenges still exist, especially when optimizing LC separation techniques for assays that include analytes with differing chemical properties. Here, we have identified seven multi-analyte assays for first-line anti-TB drugs that use various solvents for sample preparation and mobile phase separation. Only two multi-analyte assays for second-line anti-TB drugs were identified (including either nine or 20 analytes), with each using different protein precipitation methods, mobile phases and columns. The 20 analyte assay did not include bedaquiline, delamanid, meropenem or imipenem. For these drugs, other assays with similar methodologies were identified that could be incorporated in the development of a future comprehensive multi-analyte assay. TDM is a powerful methodology for monitoring patient\'s individual treatments in TB programmes, but its implementation will require different approaches depending on available resources. Since TB is most-prevalent in low- and middle-income countries where resources are scarce, a patient-centred approach using sampling methods other than large volume blood draws, such as dried blood spots or saliva collection, could facilitate its adoption and use. Regardless of the methodology of collection and analysis, it will be critical that laboratory proficiency programmes are in place to ensure adequate quality control. It is our intent that the information contained in this review will contribute to the process of assembling comprehensive multiplexed assays for the dynamic monitoring of anti-TB drug treatment in affected individuals.
摘要：
治疗药物监测（TDM）使用药物浓度，主要来自血浆，优化药物剂量。优化药物剂量可以改善治疗结果，降低毒性，降低获得性耐药的风险。这篇叙述性综述的目的是通过回顾该领域的现有文献，概述和讨论使用液相色谱-串联质谱（LC-MS/MS）开发抗结核（TB）药物的多分析物测定法的挑战。与其他分析方法相比，LC-MS/MS提供更高的灵敏度和选择性,同时需要相对低的样品体积。此外,多分析物测定更容易进行，因为即使使用非选择性样品制备技术，也可以进行足够的分离和短的运行时间。然而,挑战依然存在,特别是当优化LC分离技术用于包括具有不同化学性质的分析物的测定时。这里,我们已经确定了7种用于一线抗结核药物的多分析物检测方法,这些药物使用各种溶剂进行样品制备和流动相分离.仅鉴定了两种用于二线抗结核药物的多分析物测定法（包括9种或20种分析物）。每个都使用不同的蛋白质沉淀方法，流动相和柱。20种分析物测定不包括bedaquiline，Delamanid,美罗培南或亚胺培南。对于这些药物,确定了具有类似方法的其他测定法，可以将其纳入未来的综合多分析物测定法的开发中。TDM是在结核病项目中监测患者个体治疗的强大方法，但它的实施将需要不同的方法取决于可用的资源。由于结核病在资源匮乏的低收入和中等收入国家最为普遍，以患者为中心的方法，使用大量抽血以外的采样方法，如干燥的血斑或唾液收集，可以促进其采用和使用。不管收集和分析的方法如何，至关重要的是，必须制定实验室能力计划，以确保适当的质量控制。我们的目的是，本综述中包含的信息将有助于组装全面的多重检测方法，以动态监测受影响的个体的抗结核药物治疗。
