Automated DBS-online SPE–LC–MS/MS platform with dynamic solvent dilution: Robust quantification of antipsychotic drugs for decentralized therapeutic drug monitoring

IF 2.8 3区医学 Q2 BIOCHEMICAL RESEARCH METHODS

Journal of Chromatography B Pub Date : 2025-06-19 DOI:10.1016/j.jchromb.2025.124704

Yanxiao Zhou , Huirong Li , Mengjia Lin , Jiwei Yang , Xiaofeng Yu

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引用次数: 0

Abstract

This study introduces a novel fully automated dried blood spot (DBS)-online solid-phase extraction (SPE)-LC-MS/MS system for the quantification of 19 antipsychotic drugs in dried blood spots, addressing critical challenges in therapeutic drug monitoring (TDM). By integrating dynamic online dilution technology, the system overcomes solvent incompatibility between DBS eluents (high organic content) and hydrophilic SPE sorbents, minimizing analyte loss during trapping. Moreover, the automated workflow eliminates manual intervention, achieving precision (CV ≤12 %), accuracy (RE ≤ ±10 %) and matrix-agnostic performance (ME%: −11.4 %–10.8 %, CV <10 %). When validated across serum and whole blood matrices, the method demonstrated exceptional linearity (R² > 0.99) and sensitivity (LOD: 0.01–0.71 ng/mL). Stability studies confirmed DBS integrity at extreme temperatures (40 °C to 2–8 °C), enabling cost-effective sample transport via standard postal services. Comparative analysis with offline LC–MS–MS revealed strong agreement, underscoring the method's equivalence to gold-standard techniques. The platform's automation, minimal matrix dependency, and robustness position it as a transformative solution for decentralized TDM, particularly in resource-limited settings

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动态溶剂稀释的全自动dbs在线SPE-LC-MS /MS平台：用于分散治疗药物监测的抗精神病药物的稳健定量

本研究介绍了一种新的全自动干血点(DBS)-在线固相萃取(SPE)-LC-MS/MS系统，用于定量干血点中19种抗精神病药物，解决了治疗药物监测（TDM）的关键挑战。通过集成动态在线稀释技术，该系统克服了DBS洗脱剂（高有机含量）与亲水SPE吸附剂之间的溶剂不相容性，最大限度地减少了捕获过程中分析物的损失。此外，自动化工作流程消除了人工干预，实现了精密度（CV≤12%）、准确度（RE≤±10%）和矩阵不可知性能（ME%:−11.4% - 10.8%,CV < 10%）。当在血清和全血基质中验证时，该方法表现出优异的线性(R2 >；0.99)，灵敏度（LOD: 0.01 ~ 0.71 ng/mL）。稳定性研究证实了DBS在极端温度（40°C至2-8°C）下的完整性，使通过标准邮政服务的样品运输具有成本效益。与离线LC-MS-MS的对比分析显示了强烈的一致性，强调了该方法与金标准技术的等效性。该平台的自动化、最小矩阵依赖和鲁棒性使其成为分散式TDM的变革性解决方案，特别是在资源有限的环境中

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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.