<i>In vivo</i> solid phase microextraction for therapeutic monitoring and pharmacometabolomic fingerprinting of lung during <i>in vivo</i> lung perfusion of FOLFOX

Nikita Looby; Anna Roszkowska; Miao Yu; German Rios-Gomez; Mauricio Pipkin; Barbara Bojko; Marcelo Cypel; Janusz Pawliszyn

doi:10.1016/j.jpha.2023.04.005

Volume 13 Issue 10

Oct. 2023

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Article Navigation > Journal of Pharmaceutical Analysis > 2023 > 13(10): 1195-1204

Nikita Looby, Anna Roszkowska, Miao Yu, German Rios-Gomez, Mauricio Pipkin, Barbara Bojko, Marcelo Cypel, Janusz Pawliszyn. In vivo solid phase microextraction for therapeutic monitoring and pharmacometabolomic fingerprinting of lung during in vivo lung perfusion of FOLFOX[J]. Journal of Pharmaceutical Analysis, 2023, 13(10): 1195-1204. doi: 10.1016/j.jpha.2023.04.005

Citation:

Nikita Looby, Anna Roszkowska, Miao Yu, German Rios-Gomez, Mauricio Pipkin, Barbara Bojko, Marcelo Cypel, Janusz Pawliszyn. In vivo solid phase microextraction for therapeutic monitoring and pharmacometabolomic fingerprinting of lung during in vivo lung perfusion of FOLFOX[J]. Journal of Pharmaceutical Analysis, 2023, 13(10): 1195-1204. doi: 10.1016/j.jpha.2023.04.005

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In vivo solid phase microextraction for therapeutic monitoring and pharmacometabolomic fingerprinting of lung during in vivo lung perfusion of FOLFOX

doi: 10.1016/j.jpha.2023.04.005

a. Department of Chemistry, University of Waterloo, 200 University Avenue West, Waterloo, ON, N2L 3G1, Canada;
b. Department of Pharmaceutical Chemistry, Medical University of Gdansk, 80-416, Gdansk, Poland;
c. Division of Thoracic Surgery, University Health Network, TGH, 200 Elizabeth St, Toronto, ON, M5G 2C4, Canada;
d. Department of Pharmacodynamics and Molecular Pharmacology, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-089, Bydgoszcz, Poland

Funds:

We would like to thank our collaborators at Millipore Sigma for providing us with the SPME fibers used in this work. We are grateful to the Canadian Institutes of Health Research (CIHR) – Natural Sciences and Engineering Research Council (NSERC) of the Canada Collaborative Health Research Projects program for their financial support (Grant No.: 355935) and the Natural Sciences and Engineering Research Council of Canada Industrial Research Chair (IRC) program.

Received Date: Sep. 04, 2022
Accepted Date: Apr. 08, 2023
Rev Recd Date: Apr. 04, 2023
Publish Date: Oct. 30, 2023

Abstract

Abstract

In vivo lung perfusion (IVLP) is a novel isolated lung technique developed to enable the local, in situ administration of high-dose chemotherapy to treat metastatic lung cancer. Combination therapy using folinic acid (FOL), 5-fluorouracil (F), and oxaliplatin (OX) (FOLFOX) is routinely employed to treat several types of solid tumours in various tissues. However, F is characterized by large interpatient variability with respect to plasma concentration, which necessitates close monitoring during treatments using of this compound. Since plasma drug concentrations often do not reflect tissue drug concentrations, it is essential to utilize sample-preparation methods specifically suited to monitoring drug levels in target organs. In this work, in vivo solid-phase microextraction (in vivo SPME) is proposed as an effective tool for quantitative therapeutic drug monitoring of FOLFOX in porcine lungs during pre-clinical IVLP and intravenous (IV) trials. The concomitant extraction of other endogenous and exogenous small molecules from the lung and their detection via liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS) enabled an assessment of FOLFOX's impact on the metabolomic profile of the lung and revealed the metabolic pathways associated with the route of administration (IVLP vs. IV) and the therapy itself. This study also shows that the immediate instrumental analysis of metabolomic samples is ideal, as long-term storage at -80 °C results in changes in the metabolite content in the sample extracts.
- In vivo lung perfusion,
- Solid-phase microextraction,
- Chemotherapy,
- Metabolomics,
- Therapeutic drug monitoring

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References(36)

References

J.L. Fischel, P. Formento, J. Ciccolini, et al., Impact of the oxaliplatin-5 fluorouracil-folinic acid combination on respective intracellular determinants of drug activity, Br. J. Cancer 86 (2002) 1162-1168.

P.M. Wilson, P.V. Danenberg, P.G. Johnston, et al., Standing the test of time: Targeting thymidylate biosynthesis in cancer therapy, Nat. Rev. Clin. Oncol. 11 (2014) 282-298.

P.V. Danenberg, B. Gustavsson, P. Johnston, et al., Folates as adjuvants to anticancer agents: Chemical rationale and mechanism of action, Crit. Rev. Oncol. Hematol. 106 (2016) 118-131.

F. Goirand, F. Lemaitre, M. Launay, et al., How can we best monitor 5-FU administration to maximize benefit to risk ratio? Expert Opin. Drug Metab. Toxicol. 14 (2018) 1303-1313.

P.R. Dos Santos, J. Sakamoto, M. Chen, et al., Modified InVivo lung perfusion for local chemotherapy: A preclinical study with doxorubicin, Ann. Thorac. Surg. 101 (2016) 2132-2140.

P.R. dos Santos, I. Iskender, T. Machuca, et al., Modified in vivo lung perfusion allows for prolonged perfusion without acute lung injury, J. Thorac. Cardiovasc. Surg. 147 (2014) discussion781-discussion782.

K. Miura, M. Kinouchi, K. Ishida, et al., 5-FU metabolism in cancer and orally-administrable 5-FU drugs, Cancers 2 (2010) 1717-1730.

A.M. Di Francesco, A. Ruggiero, R. Riccardi, Cellular and molecular aspects of drugs of the future: Oxaliplatin, Cell. Mol. Life Sci. 59 (2002) 1914-1927.

M.W. Saif, A. Choma, S.J. Salamone, et al., Pharmacokinetically guided dose adjustment of 5-fluorouracil: A rational approach to improving therapeutic outcomes, J. Natl. Cancer Inst. 101 (2009) 1543-1552.

D.M. Bach, J.A. Straseski, W. Clarke, Therapeutic drug monitoring in cancer chemotherapy, Bioanalysis 2 (2010) 863-879.

Y.J. Xue, H. Gao, Q.C. Ji, et al., Bioanalysis of drug in tissue: Current status and challenges, Bioanalysis 4 (2012) 2637-2653.

J. Rattner, O.F. Bathe, Monitoring for response to antineoplastic drugs: The potential of a metabolomic approach, Metabolites 7 (2017), 60.

O. Fiehn, Metabolomics: The link between genotypes and phenotypes, Plant Mol. Biol. 48 (2002) 155-171.

A.D. Eckhart, K. Beebe, M. Milburn, Metabolomics as a key integrator for omic advancement of personalized medicine and future therapies, Clin. Transl. Sci. 5 (2012) 285-288.

D. Vuckovic, X. Zhang, E. Cudjoe, et al., Solid-phase microextraction in bioanalysis: New devices and directions, J. Chromatogr. A 1217 (2010) 4041-4060.

B. Bojko, J. Pawliszyn, In vivo and ex vivo SPME: A low invasive sampling and sample preparation tool in clinical bioanalysis, Bioanalysis 6 (2014) 1227-1239.

E. Cudjoe, B. Bojko, P. Togunde, et al., In vivo solid-phase microextraction for tissue bioanalysis, Bioanalysis 4 (2012) 2605-2619.

N. Reyes-Garces, E. Gionfriddo, G.A. Gomez-Rios, et al., Advances in solid phase microextraction and perspective on future directions, Anal. Chem. 90 (2018) 302-360.

B. Bojko, N. Reyes-Garces, V. Bessonneau, et al., Solid-phase microextraction in metabolomics, Trac Trends Anal. Chem. 61 (2014) 168-180.

D. Vuckovic, J. Pawliszyn, Systematic evaluation of solid-phase microextraction coatings for untargeted metabolomic profiling of biological fluids by liquid chromatography-mass spectrometry, Anal. Chem. 83 (2011) 1944-1954.

J. Deng, Y. Yang, X. Wang, et al., Strategies for coupling solid-phase microextraction with mass spectrometry, Trac Trends Anal. Chem. 55 (2014) 55-67.

N.T. Looby, M. Tascon, V.R. Acquaro, et al., Solid phase microextraction coupled to mass spectrometry via a microfluidic open interface for rapid therapeutic drug monitoring, Anal. 144 (2019) 3721-3728.

M.M. Swindle, Second edition: Swine in the laboratory: Surgery, anesthesia, imaging, and experimental techniques, 2nd edition, Taylor&Francis Group, 2007.

A. Roszkowska, M. Tascon, B. Bojko, et al., Equilibrium ex vivo calibration of homogenized tissue for in vivo SPME quantitation of doxorubicin in lung tissue, Talanta 183 (2018) 304-310.

M. Tascon, G.A. Gomez-Rios, N. Reyes-Garces, et al., Ultra-fast quantitation of voriconazole in human plasma by coated blade spray mass spectrometry, J. Pharm. Biomed. Anal. 144 (2017) 106-111.

S. Lendor, G.A. Gomez-Rios, E. Boyaci, et al., Space-resolved tissue analysis by solid-phase microextraction coupled to high-resolution mass spectrometry via desorption electrospray ionization, Anal. Chem. 91 (2019) 10141-10148.

M.C. Chambers, B. MacLean, R. Burke, et al., A cross-platform toolkit for mass spectrometry and proteomics, Nat. Biotechnol. 30 (2012) 918-920.

C.A. Smith, E.J. Want, G. O’Maille, et al., XCMS: Processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification, Anal. Chem. 78 (2006) 779-787.

A. Roszkowska, M. Yu, V. Bessonneau, et al., Tissue storage affects lipidome profiling in comparison to in vivo microsampling approach, Sci. Rep. 8 (2018), 6980.

K. Uppal, D.I. Walker, D.P. Jones, xMSannotator: An R package for network-based annotation of high-resolution metabolomics data, Anal. Chem. 89 (2017) 1063-1067.

T. Alcindor, N. Beauger, Oxaliplatin: A review in the era of molecularly targeted therapy, Curr. Oncol. 18 (2011) 18-25.

D.S. Wishart, Y.D. Feunang, A.C. Guo, et al., DrugBank 5.0: A major update to the DrugBank database for 2018, Nucleic Acids Res. 46 (2018) D1074-D1082.

D.G. Priest, J.C. Schmitz, M.A. Bunni, et al., Pharmacokinetics of leucovorin metabolites in human plasma as a function of dose administered orally and intravenously, J. Natl. Cancer Inst. 83 (1991) 1806-1812.

J.A. Straw, D. Szapary, W.T. Wynn, Pharmacokinetics of the diastereoisomers of leucovorin after intravenous and oral administration to normal subjects, Cancer Res. 44 (1984) 3114-3119.

V. De Brouwer, G. Zhang, S. Storozhenko, et al., pH stability of individual folates during critical sample preparation steps in prevision of the analysis of plant folates, Phytochem. Anal. 18 (2007) 496-508.

A. Ariel, C.N. Serhan, Resolvins and protectins in the termination program of acute inflammation, Trends Immunol. 28 (2007) 176-183.

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