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dc.contributor.authorRoszkowska, Anna
dc.contributor.authorTascon, Marcos
dc.contributor.authorBojko, Barbara
dc.contributor.authorGoryński, Krzysztof
dc.contributor.authordos Santos, Pedro Reck
dc.contributor.authorCypel, Marcelo
dc.contributor.authorPawliszyn, Janusz 16:58:01 (GMT) 16:58:01 (GMT)
dc.descriptionThe final publication is available at Elsevier via © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license
dc.description.abstractThe fast and sensitive determination of concentrations of anticancer drugs in specific organs can improve the efficacy of chemotherapy and minimize its adverse effects. In this paper, ex vivo solid-phase microextraction (SPME) coupled to LC-MS/MS as a method for rapidly quantitating doxorubicin (DOX) in lung tissue was optimized. Furthermore, the theoretical and practical challenges related to the real-time monitoring of DOX levels in the lung tissue of a living organism (in vivo SPME) are presented. In addition, several parameters for ex vivo/in vivo SPME studies, such as extraction efficiency of autoclaved fibers, intact/homogenized tissue differences, critical tissue amount, and the absence of an internal standard are thoroughly examined. To both accurately quantify DOX in solid tissue and minimize the error related to the lack of an internal standard, a calibration method at equilibrium conditions was chosen. In optimized ex vivo SPME conditions, the targeted compound was extracted by directly introducing a 15 mm (45 µm thickness) mixed-mode fiber into 15 g of homogenized tissue for 20 min, followed by a desorption step in an optimal solvent mixture. The detection limit for DOX was 2.5 µg g−1 of tissue. The optimized ex vivo SPME method was successfully applied for the analysis of DOX in real pig lung biopsies, providing an averaged accuracy and precision of 103.2% and 12.3%, respectively. Additionally, a comparison between SPME and solid-liquid extraction revealed good agreement. The results presented herein demonstrate that the developed SPME method radically simplifies the sample preparation step and eliminates the need for tissue biopsies. These results suggest that SPME can accurately quantify DOX in different tissue compartments and can be potentially useful for monitoring and adjusting drug dosages during chemotherapy in order to achieve effective and safe concentrations of doxorubicin.en
dc.description.sponsorshipNatural Sciences and Engineering Research Council (NSERC) of Canadaen
dc.description.sponsorshipCanadian Institutes of Health Research (CIHR) [grant 355935]en
dc.description.sponsorshipSK CIHR (grant 190953)en
dc.description.sponsorshipGL2 (grant GL2-01-019)en
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.subjectSPME calibrationen
dc.subjectTherapeutic drug monitoringen
dc.titleEquilibrium ex vivo calibration of homogenized tissue for in vivo SPME quantitation of doxorubicin in lung tissueen
dcterms.bibliographicCitationRoszkowska, A., Tascon, M., Bojko, B., Goryński, K., dos Santos, P. R., Cypel, M., & Pawliszyn, J. (2018). Equilibrium ex vivo calibration of homogenized tissue for in vivo SPME quantitation of doxorubicin in lung tissue. Talanta, 183, 304–310.
uws.contributor.affiliation1Faculty of Scienceen

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