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Ultrasensitive Tracking of Dual Antiparasitics in Living Tissues: UPLC-MS/MS Reveals Synergistic Distribution of Oxyclozanide and Levamisole Hydrochloride

文献类型： 外文期刊

作者： Dai, Guonian;Zhou, Yaxin;Xu, Jing;Sun, Kairui;Li, Haiquan;Wang, Qing;Li, Bing;Zhou, Xuzheng;Zhang, Jiyu

作者机构：

期刊名称： ANALYTICAL CHEMISTRY

ISSN： 0003-2700

年卷期： 2026 年

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收录情况： SCIE（2025版） ; ; EI（2025版） ; ; Nature Index（2023版）

摘要： This study addresses the critical gap in tissue distribution kinetics of veterinary anthelmintic combination therapies by developing a novel dual-mode dynamic-switching ultraperformance liquid chromatography coupled with triple quadrupole tandem mass spectrometry (UPLC-MS/MS) method with ultrahigh sensitivity (limit of detection, LOD = 0.5 ng/g). The method enables synchronous quantification of oxyclozanide (OXY, logP = 5.69) and levamisole hydrochloride (LEV, logP = 2.32) in complex biological matrices through optimized ESI+/ESI- ionization and antiadsorption chromatographic separation (BEH C18 column). Validated per VICH GL49 and EMA/ICH guidelines, the assay demonstrated excellent linearity (2-800 ng/g, R-2 > 0.990), precision (relative standard deviation, RSD <= 10.32%), and recovery (91.41-102.49%) across nine tissues. Spatiotemporal profiling in rats revealed distinct pharmacokinetic synergies: OXY exhibited prolonged gastric retention (maximum concentration, C-max = 5377 ng/g, half-life, t(1/2) = 32-48 h) and fecal-dominated excretion (94.58%), while LEV achieved systemic distribution with blood-brain barrier penetration (brain C-max = 501 ng/g) and renal clearance (57.88%). The three-dimensional complementarity (spatial targeting, temporal kinetics, and clearance pathways) provides a mechanistic basis for enhanced anthelmintic efficacy and informs the optimization of withdrawal periods. This work establishes a paradigm for the preclinical evaluation of veterinary drug combinations.

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