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Solid phase microextraction chemical biopsy tool for monitoring of doxorubicin residue during in vivo lung chemo-perfusion

引用

Journal of Pharmaceutical Analysis 2021年第1期11卷 37-47页

作者： Barbara Bojko Nikita Looby Mariola Olkowicz Anna Roszkowska bogumiła kupcewicz Pedro Reck dos Santos Khaled Ramadan Shaf Keshavjee Thomas K.Waddell German Goomez-Rios Marcos Tascon Krzysztof Gorynski Marcelo Cypel Janusz Pawliszyn Department of Chemistry University of WaterlooWaterlooON M1B 6G3Canada Department of Pharmacodynamics and Molecular Pharmacology Faculty of PharmacyCollegium Medicum in BydgoszczNicolaus Copernicus University in Torun85-089BydgoszczPoland Jagiellonian Centre for Experimental Therapeutics(JCET) Jagiellonian University30-348 KrakowPoland Department of Pharmaceutical Chemistry Medical University of Gdansk80-416GdanskPoland Department of Inorganic and Analytical Chemistry Faculty of PharmacyCollegium Medicum in BydgoszczNicolaus Copernicus University in Torun85-089BydgoszczPoland University Health Network-TGH TorontoON M5G 2C4Canada

Development of a novel in vivo lung perfusion(IVLP)procedure allows localized delivery of high-dose doxorubicin(DOX)for targeting residual micrometastatic disease in the ***,DOX delivery via IVLP requires careful monitoring of drug level to ensure tissue concentrations of this agent remain in the therapeutic window.A small dimension nitinol wire coated with a sorbent of biocompatible morphology(Bio-SPME)has been clinically evaluated for in vivo lung tissue extraction and determination of DOX and its key *** in vivo Bio-SPME-IVLP experiments were performed on pig model over various(150 and 225 mg/m^(2))drug doses,and during human clinical *** patients with metastatic osteosarcoma were treated with a single 5 and 7 μg/mL(respectively)dose of DOX during a 3-h *** both pig and human cases,DOX tissue levels presented similar trends during *** lung tissue concentrations of drug ranged between 15 and 293 μg/g over the course of the IVLP *** addition to DOX levels,Bio-SPME followed by liquid chromatography-mass spectrometry analysis generated 64 metabolic features during endogenous metabolite screening,providing information about lung status during drug ***-time monitoring of DOX levels in the lungs can be performed effectively throughout the IVLP procedure by in vivo Bio-SPME chemical biopsy ***-SPME also extracted various endogenous molecules,thus providing a real-time snapshot of the physiology of the cells,which might assist in the tailoring of personalized treatment strategy.

关键词： In vivo solid phase microextraction Metabolite profiling Spatial resolution Therapeutic drug monitoring Tissue analysis

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