Volume 11 Issue 1
Feb.  2021
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Barbara Bojko, Nikita Looby, Mariola Olkowicz, Anna Roszkowska, Bogumiła Kupcewicz, Pedro Reck dos Santos, Khaled Ramadan, Shaf Keshavjee, Thomas K. Waddell, German Gómez-Ríos, Marcos Tascon, Krzysztof Goryński, Marcelo Cypel, Janusz Pawliszyn. Solid phase microextraction chemical biopsy tool for monitoring of doxorubicin residue during in vivo lung chemo-perfusion[J]. Journal of Pharmaceutical Analysis, 2021, 11(1): 37-47. doi: 10.1016/j.jpha.2020.08.011
Citation: Barbara Bojko, Nikita Looby, Mariola Olkowicz, Anna Roszkowska, Bogumiła Kupcewicz, Pedro Reck dos Santos, Khaled Ramadan, Shaf Keshavjee, Thomas K. Waddell, German Gómez-Ríos, Marcos Tascon, Krzysztof Goryński, Marcelo Cypel, Janusz Pawliszyn. Solid phase microextraction chemical biopsy tool for monitoring of doxorubicin residue during in vivo lung chemo-perfusion[J]. Journal of Pharmaceutical Analysis, 2021, 11(1): 37-47. doi: 10.1016/j.jpha.2020.08.011

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

doi: 10.1016/j.jpha.2020.08.011
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We would like to thank our collaborators at Millipore/Sigma for kindly providing us with the fibers and chromatographic columns employed for this investigation. We would also like to thank Thermo Fisher Scientific for lending us the triple quadrupole mass spectrometer that was used in this work (TSQ Quantiva).

  • Received Date: Apr. 15, 2020
  • Accepted Date: Aug. 24, 2020
  • Rev Recd Date: Aug. 24, 2020
  • Available Online: Jan. 24, 2022
  • Publish Date: Feb. 15, 2021
  • 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.
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