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dc.contributor.author
Ladetto, María Florencia  
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Lazaro Martinez, Juan Manuel  
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Brito Devoto, Tomás  
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Briceño, Victor  
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Castro, Guillermo Raul  
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Cuestas, María Luján  
dc.date.available
2024-01-18T10:01:42Z  
dc.date.issued
2023-01  
dc.identifier.citation
Ladetto, María Florencia; Lazaro Martinez, Juan Manuel; Brito Devoto, Tomás; Briceño, Victor; Castro, Guillermo Raul; et al.; Quantitative determination of voriconazole by thionine reduction and its potential application in a pharmaceutical and clinical setting; Royal Society of Chemistry; Analytical Methods; 15; 9; 1-2023; 1230-1240  
dc.identifier.issn
1759-9660  
dc.identifier.uri
http://hdl.handle.net/11336/224031  
dc.description.abstract
Voriconazole (VCZ) is a triazolic drug used to treat serious fungal infections and invasive mycosis and has also been more recently used as a generic antifungal treatment. However, VCZ therapies can cause undesirable side effects and doses must be carefully monitored before administration to avoid or reduce severe toxic effects. Analytical techniques used to quantify VCZ are mostly based on HPLC/UV and often associated with multiple technical steps as well as expensive equipment. The present work aimed to develop an accessible and affordable spectrophotometric technique in the visible range (λ = 514 nm) for the simple quantification of VCZ. The technique was based on VCZ-induced reduction of thionine (TH, red) to leucothionine (LTH, colorless) under alkaline conditions. The reaction showed a linear correlation over the range of 1.00 μg mL−1 to 60.00 μg mL−1 at room temperature, the limits of detection and quantification being 1.93 μg mL−1 and 6.45 μg mL−1, respectively. VCZ degradation products (DPs) according to 1H and 13C-NMR spectrometric determinations not only showed good agreement with the ones previously reported (DP1 and DP2 - T. M. Barbosa, G. A. Morris, M. Nilsson, R. Rittner and C. F. Tormena, RSC Adv., 2017, DOI: 10.1039/c7ra03822d), but also revealed a new degradation product (DP3). Mass spectrometry not only confirmed the presence of LTH as a result of the VCZ DP-induced TH reduction, but also revealed the formation of a novel and stable Schiff base as a reaction product between DP1 and LTH. The latter finding became significant as it stabilizes the reaction for quantification purposes, by hindering LTH ↔TH redox reversibility. This analytical method was then validated according to the ICH Q2 (R1) guidelines, and additionally, it could be demonstrated as applicable for the reliable VCZ quantification in commercially available tablets. Importantly, it also represents a useful tool for detecting toxic threshold concentrations in human plasma from VCZ-treated patients, alerting when these risky limits are exceeded. In this way, this technique independent from sophisticated equipment, highly qualifies as a low-cost, reproducible, trustable, and non-laborious alternative method for VCZ measurements from different matrices.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Royal Society of Chemistry  
dc.rights
info:eu-repo/semantics/restrictedAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
VORICONAZOLE  
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THIONINE  
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SPECTROPHOTOMETRY  
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VORICONAZOLE DEGRADATION  
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MASS SPECTROSCOPY  
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SCHIFF BASE  
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Otras Ciencias Químicas  
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Ciencias Químicas  
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CIENCIAS NATURALES Y EXACTAS  
dc.title
Quantitative determination of voriconazole by thionine reduction and its potential application in a pharmaceutical and clinical setting  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2024-01-08T14:16:06Z  
dc.identifier.eissn
1759-9679  
dc.journal.volume
15  
dc.journal.number
9  
dc.journal.pagination
1230-1240  
dc.journal.pais
Reino Unido  
dc.description.fil
Fil: Ladetto, María Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina  
dc.description.fil
Fil: Lazaro Martinez, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Metabolismo del Fármaco. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Metabolismo del Fármaco; Argentina  
dc.description.fil
Fil: Brito Devoto, Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina  
dc.description.fil
Fil: Briceño, Victor. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina  
dc.description.fil
Fil: Castro, Guillermo Raul. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigación y Desarrollo en Fermentaciones Industriales. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Investigación y Desarrollo en Fermentaciones Industriales; Argentina  
dc.description.fil
Fil: Cuestas, María Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; Argentina  
dc.journal.title
Analytical Methods  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://pubs.rsc.org/en/content/articlelanding/2023/ay/d2ay01431a/unauth  
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info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1039/D2AY01431A