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

• Published in: Journal of pharmaceutical analysis 2021-02, Vol.11 (1), p.37-47
• Main Authors: Bojko, Barbara, Looby, Nikita, Olkowicz, Mariola, Roszkowska, Anna, Kupcewicz, Bogumiła, Reck dos Santos, Pedro, Ramadan, Khaled, Keshavjee, Shaf, Waddell, Thomas K., Gómez-Ríos, German, Tascon, Marcos, Goryński, Krzysztof, Cypel, Marcelo, Pawliszyn, Janusz
• Format: Article
• Language: English
• Subjects: Biocompatibility; Biodistribution; Biopsy; Bone cancer; Chromatography; Clinical trials; Doxorubicin; Drug dosages; In vivo solid phase microextraction; Laboratories; Liquid chromatography; Lung diseases; Lungs; Mass spectrometry; Mass spectroscopy; Metabolite profiling; Metabolites; Metastases; Metastasis; Original; Osteosarcoma; Patients; Perfusion; Scientific imaging; Solid phase methods; Spatial resolution; Therapeutic drug monitoring; Tissue analysis; Trends
• ISSN: 2095-1779; 2214-0883
• DOI: 10.1016/j.jpha.2020.08.011

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. [Display omitted] •A minimally invasive Bio-SPME chemical biopsy sampling tool was proposed for DOX quantification throughout IVLP.•SPME probes enabled analytes’ extraction not causing tissue injury nor disrupting the equilibrium of the living system.•The level and biodistribution of the drug in the lung were monitored together with metabolites associated with its activity.