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

Journal of Pharmaceutical Analysis

Khaled Ramadan¹  Nikita Looby²  Bogumiła Kupcewicz³  Mariola Olkowicz⁴  Anna Roszkowska⁴  Barbara Bojko⁴  Marcelo Cypel⁴  Pedro Reck dos Santos⁴  Janusz Pawliszyn⁴  Shaf Keshavjee⁵  Marcos Tascon⁶  Krzysztof Goryński⁶  German Gómez-Ríos⁶  Thomas K. Waddell⁶ 

[1] Department of Pharmaceutical Chemistry, Medical University of Gdansk, 80-416, Gdansk, Poland;Department of Pharmacodynamics and Molecular Pharmacology, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-089, Bydgoszcz, Poland;Jagiellonian Centre for Experimental Therapeutics (JCET), Jagiellonian University, 30-348 Krakow, Poland;Department of Chemistry, University of Waterloo, Waterloo, ON M1B 6G3, Canada;Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-089, Bydgoszcz, Poland;University Health Network - TGH, Toronto, ON M5G 2C4, Canada;

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

DOI  :  

来源: DOAJ

【 摘 要 】

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 lungs. However, 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 metabolites. The in vivo Bio-SPME-IVLP experiments were performed on pig model over various (150 and 225 mg/m2) drug doses, and during human clinical trial. Two patients with metastatic osteosarcoma were treated with a single 5 and 7 μg/mL (respectively) dose of DOX during a 3-h IVLP. In both pig and human cases, DOX tissue levels presented similar trends during IVLP. Human lung tissue concentrations of drug ranged between 15 and 293 μg/g over the course of the IVLP procedure. In 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 administration. Real-time monitoring of DOX levels in the lungs can be performed effectively throughout the IVLP procedure by in vivo Bio-SPME chemical biopsy approach. Bio-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.

【 授权许可】

Unknown