Analytical and clinical validation of a volumetric absorptive microsampling (VAMS) – Ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the analysis of Clofazimine in whole blood

IF 2.8 3区医学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of Chromatography B Pub Date : 2025-01-25 DOI:10.1016/j.jchromb.2025.124482

Rhea Veda Nugraha , Vycke Yunivita , Prayudi Santoso , Aliya Nur Hasanah , Triana Nurul Meirina , Atu Purnama Dewi , Harold Eka Atmaja , Lindsey te Brake , Rob E. Aarnoutse , Rovina Ruslami

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引用次数: 0

Abstract

Monitoring clofazimine blood concentrations is crucial for preventing treatment failure in patients with Multidrug-resistant Tuberculosis (MDR-TB). Volumetric Absorptive Microsampling (VAMS) offers a practical alternative to Conventional Venous Sampling (CVS), enabling remote sampling. Samples collected via VAMS can be conveniently transported to laboratories via courier, enhancing accessibility and patient compliance. In this study, we developed and validated an analytical method for quantifying clofazimine in whole blood collected using VAMS. The study compared the performance and cost-effectiveness of VAMS with CVS. A total of 55 matched finger-prick VAMS and CVS samples were obtained from 39 MDR-TB patients and analyzed using validated UPLC-MS/MS assays. Clofazimine concentrations collected via VAMS and CVS were compared using Passing-Bablok regression, while bias and overall agreement were evaluated through Bland-Altman analysis. Passing-Bablok regression revealed no significant constant difference between VAMS and CVS (95% CI slope: 0.7627–0.9573; 95% CI intercept: −0.02141–0.06482), but systematic difference of 13% lower clofazimine concentrations was observed in VAMS compared to plasma. Bland-Altman analysis demonstrated moderate agreement, with mean plasma/VAMS ratio of 0.9457 (95% CI: 0.88358–1.00775) and 95% Limits of Agreement (LoA) ranging from 0.4956 (95% CI: 0.38881–0.60230) to 1.3858 (95% CI: 1.28903–1.50252). Although statistically significant bias was identified, applying correction factors could improve interchangeability between the two techniques. Furthermore, VAMS was more cost-effective than CVS, with approximate cost difference of 4.45 USD per sample. These findings suggest that VAMS sampling has the potential to replace CVS for routine clinical monitoring of clofazimine, offering a more accessible and economical approach.

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来源期刊

Journal of Chromatography B 医学-分析化学

CiteScore

5.60

自引率

3.30%

发文量

306

审稿时长

44 days

期刊介绍： The Journal of Chromatography B publishes papers on developments in separation science relevant to biology and biomedical research including both fundamental advances and applications. Analytical techniques which may be considered include the various facets of chromatography, electrophoresis and related methods, affinity and immunoaffinity-based methodologies, hyphenated and other multi-dimensional techniques, and microanalytical approaches. The journal also considers articles reporting developments in sample preparation, detection techniques including mass spectrometry, and data handling and analysis. Developments related to preparative separations for the isolation and purification of components of biological systems may be published, including chromatographic and electrophoretic methods, affinity separations, field flow fractionation and other preparative approaches. Applications to the analysis of biological systems and samples will be considered when the analytical science contains a significant element of novelty, e.g. a new approach to the separation of a compound, novel combination of analytical techniques, or significantly improved analytical performance.