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Mass spectrometry for therapeutic drug monitoring of anti-tuberculosis drugs

Kuhlin, J., Sturkenboom, M. G. G., Ghimire, S., Margineanu, I., Elsen, S. H. J. V. D., Simbar, N., Akkerman, O. W., Jongedijk, E. M., Koster, R. A., Bruchfeld, J., Touw, D. J. & Alffenaar, J-W. C., Sep-2019, In : Clinical Mass Spectrometry. 14, Part A, p. 34-45 12 p.

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  • Mass spectrometry for therapeutic drug monitoring of anti-tuberculosis drugs

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DOI

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.
Original languageEnglish
Pages (from-to)34-45
Number of pages12
JournalClinical Mass Spectrometry
Volume14
Issue numberPart A
Early online date19-Oct-2018
Publication statusPublished - Sep-2019

    Keywords

  • Tuberculosis, Liquid chromatography, LC-MS/MS, TDM, Multi-analyte assays

ID: 71880262