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 : 2025-03-01 Epub 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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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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体积吸收微进样(VAMS) -超高效液相色谱-串联质谱（UPLC-MS/MS）分析全血中氯法齐明的分析和临床验证。

监测氯法齐明血药浓度对于预防耐多药结核病（MDR-TB）患者治疗失败至关重要。体积吸收微采样（VAMS）提供了一个实用的替代传统静脉采样（CVS），使远程采样。通过VAMS采集的样品可以通过快递方便地运送到实验室，提高了可及性和患者依从性。在这项研究中，我们建立并验证了一种用VAMS定量全血氯法齐明的分析方法。本研究比较了VAMS和CVS的性能和成本效益。从39例耐多药结核病患者中获得55份相匹配的手指穿刺VAMS和CVS样本，并使用经过验证的UPLC-MS/MS分析。通过VAMS和CVS收集的氯法齐明浓度使用pass - bablok回归进行比较，通过Bland-Altman分析评估偏倚和总体一致性。Passing-Bablok回归显示VAMS与CVS无显著性差异(95% CI斜率：0.7627-0.9573；95% CI截距：-0.02141-0.06482)，但与血浆相比，VAMS中氯法齐明浓度降低了13%。Bland-Altman分析显示中度一致，平均血浆/VAMS比值为0.9457 (95% CI: 0.88358-1.00775)， 95%一致限（LoA）范围为0.4956 （95% CI: 0.38881-0.60230）至1.3858 （95% CI: 1.28903-1.50252）。虽然发现了统计上显著的偏差，但应用校正因子可以提高两种技术之间的互换性。此外，VAMS比CVS更具成本效益，每个样品的成本差异约为4.45美元。这些发现表明VAMS取样有可能取代CVS进行氯法齐明的常规临床监测，提供一种更容易获得和更经济的方法。

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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.