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dc.contributor.author
Huq, Mohammad
dc.contributor.author
Tascon, Marcos
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Nazdrajic, Emir
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Roszkowska, Anna
dc.contributor.author
Pawliszyn, Janusz
dc.date.available
2021-01-29T11:33:02Z
dc.date.issued
2019-06
dc.identifier.citation
Huq, Mohammad; Tascon, Marcos; Nazdrajic, Emir; Roszkowska, Anna; Pawliszyn, Janusz; Measurement of Free Drug Concentration from Biological Tissue by Solid-Phase Microextraction: In Silico and Experimental Study; American Chemical Society; Analytical Chemistry; 91; 12; 6-2019; 7719-7728
dc.identifier.issn
0003-2700
dc.identifier.uri
http://hdl.handle.net/11336/124149
dc.description.abstract
In this article, the use of an SPME technique is reported for the first time for direct measurement of free drug concentration in solid tissue. In our investigations, we considered doxorubicin (DOX) spiked in homogenized tissue matrix at transient and equilibrium extraction conditions, with subsequent assessment of obtained experimental results by an in silico approach using mathematical models developed in COMSOL Multyphysics. In silico studies were performed on the basis of transported diluted species (tds) and reaction engineering (re) modules from COMSOL Multiphysics, using the same conditions as those used to attain experimental results. To determine the apparent binding affinity of DOX to the tissue matrix which contains multiple binding species, the experimentally determined binding affinity of DOX with human serum albumin (HSA) was considered to simplify the mathematical calculations. Here, the value of the binding affinity was considered for a single binding site and adjusted by fitting the experimental results with the mathematical model. Bovine lung tissue homogenate was selected as a surrogate matrix, and a biocompatible C-8 commercial SPME fiber was used for extraction of DOX. In total, four mathematical models were herein developed to describe the mass transfer kinetics of solid coatings: in agar gel at static conditions, in PBS solution with agitated conditions, extraction in PBS solution in the presence of an HSA binding matrix, and static extraction in homogenized lung tissue. For all conditions, simulated results were in good agreement with experimental results. The developed mathematical model allows for measurements of free drug concentrations inside the tissue matrix and facilitates calculations of local depletion of DOX by a solid SPME coating. Results of the investigations indicate that local depletion of the free form of DOX, even at the kinetic stage, is negligible for tissue extraction, as the release of the heavily bound analyte (over 99% binding to tissue matrix) is very rapid, thus easily compensating for the loss of the drug to the SPME coating. This indicates that the dissociation rate constant of DOX from lung tissue components is very rapid; therefore, the mass transfer of drug to the fiber coating via free from is very efficient. Our results also indicate that thin coating SPME fibers provide a good way to measure drug distribution after dosing, as extractions via thin coating SPME fibers do not affect the free concentration of the drug, which is responsible for drug distribution in tissue.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
American Chemical Society
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
SPME
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TISSUE ANALYSIS
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IN VIVO SAMPLING
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DRUG BINDING CONSTANT
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Química Analítica
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Ciencias Químicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Measurement of Free Drug Concentration from Biological Tissue by Solid-Phase Microextraction: In Silico and Experimental Study
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-11-16T20:03:55Z
dc.journal.volume
91
dc.journal.number
12
dc.journal.pagination
7719-7728
dc.journal.pais
Estados Unidos
dc.description.fil
Fil: Huq, Mohammad. University of Waterloo; Canadá
dc.description.fil
Fil: Tascon, Marcos. University of Waterloo; Canadá. Universidad Nacional de San Martín. Instituto de Investigación e Ingeniería Ambiental. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación e Ingeniería Ambiental; Argentina
dc.description.fil
Fil: Nazdrajic, Emir. University of Waterloo; Canadá
dc.description.fil
Fil: Roszkowska, Anna. University of Waterloo; Canadá
dc.description.fil
Fil: Pawliszyn, Janusz. University of Waterloo; Canadá
dc.journal.title
Analytical Chemistry
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1021/acs.analchem.9b00983
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