Analysis of 2′-hydroxyflavanone (2HF) in mouse whole blood by HPLC–MS/MS for the determination of pharmacokinetic parameters

Given the lack of investments, structure, and difficulty of metabolite isolation, promising natural product studies do not progress to preclinical studies, such as pharmacokinetics. 2′-Hydroxyflavanone (2HF) is a flavonoid that has shown promising results in different types of cancer and leishmanias...

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Main Authors: Luiza F. O. Gervazoni, Gabriella Gonçalves-Ozorio, Taiana Ferreira-Paes, Aline C. A. Silva, Gabriel P. E. Silveira, Heliana M. Pereira, Douglas P. Pinto, Edézio F. Cunha-Junior, Elmo E. Almeida-Amaral
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-03-01
Series:Frontiers in Chemistry
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fchem.2023.1016193/full
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author Luiza F. O. Gervazoni
Gabriella Gonçalves-Ozorio
Taiana Ferreira-Paes
Aline C. A. Silva
Gabriel P. E. Silveira
Heliana M. Pereira
Douglas P. Pinto
Edézio F. Cunha-Junior
Elmo E. Almeida-Amaral
author_facet Luiza F. O. Gervazoni
Gabriella Gonçalves-Ozorio
Taiana Ferreira-Paes
Aline C. A. Silva
Gabriel P. E. Silveira
Heliana M. Pereira
Douglas P. Pinto
Edézio F. Cunha-Junior
Elmo E. Almeida-Amaral
author_sort Luiza F. O. Gervazoni
collection DOAJ
description Given the lack of investments, structure, and difficulty of metabolite isolation, promising natural product studies do not progress to preclinical studies, such as pharmacokinetics. 2′-Hydroxyflavanone (2HF) is a flavonoid that has shown promising results in different types of cancer and leishmaniasis. For accurate quantification of 2HF in BALB/c mouse blood, a validated HPLC-MS/MS method was developed. Chromatographic analysis was performed using C18 (5μm, 150 mm × 4.6 mm). The mobile phase consisted of water containing 0.1% formic acid, acetonitrile, and methanol (35/52/13 v/v/v) at a flow rate and total running time of 0.8 mL/min and 5.50 min, respectively, with an injection volume of 20 µL. 2HF was detected by electrospray ionization in negative mode (ESI-) using multiple reaction monitoring (MRM). The validated bioanalytical method showed satisfactory selectivity without significant interference for the 2HF and IS. In addition, the concentration range between 1 and 250 ng/mL showed good linearity (r = 0.9969). The method showed satisfactory results for the matrix effect. Precision and accuracy intervals varied between 1.89% and 6.76% and 95.27% and 100.77%, respectively, fitting the criteria. No degradation of 2HF in the biological matrix was observed since stability under freezing and thawing conditions, short duration, postprocessing, and long duration showed deviations less than 15%. Once validated, the method was successfully applied in a 2HF oral pharmacokinetic study with mouse blood, and the pharmacokinetic parameters were determined. 2HF demonstrated a Cmax of 185.86 ng/mL, a Tmax of 5 min, and a half-life (T1/2) of 97.52 min.
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spelling doaj.art-4ae4d858e6ea403ba41f485dd338328f2023-03-09T04:42:16ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462023-03-011110.3389/fchem.2023.10161931016193Analysis of 2′-hydroxyflavanone (2HF) in mouse whole blood by HPLC–MS/MS for the determination of pharmacokinetic parametersLuiza F. O. Gervazoni0Gabriella Gonçalves-Ozorio1Taiana Ferreira-Paes2Aline C. A. Silva3Gabriel P. E. Silveira4Heliana M. Pereira5Douglas P. Pinto6Edézio F. Cunha-Junior7Elmo E. Almeida-Amaral8Laboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, BrazilLaboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, BrazilLaboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, BrazilLaboratório de Farmacocinética, Fundação Oswaldo Cruz, Rio de Janeiro, BrazilLaboratório de Farmacocinética, Fundação Oswaldo Cruz, Rio de Janeiro, BrazilLaboratório de Farmacocinética, Fundação Oswaldo Cruz, Rio de Janeiro, BrazilLaboratório de Farmacocinética, Fundação Oswaldo Cruz, Rio de Janeiro, BrazilLaboratório de Imunoparasitologia, Unidade Integrada de Pesquisa em Produtos Bioativos e Biociên-cias, Universidade Federal do Rio de Janeiro, Campus UFRJ, Macaé, BrazilLaboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, BrazilGiven the lack of investments, structure, and difficulty of metabolite isolation, promising natural product studies do not progress to preclinical studies, such as pharmacokinetics. 2′-Hydroxyflavanone (2HF) is a flavonoid that has shown promising results in different types of cancer and leishmaniasis. For accurate quantification of 2HF in BALB/c mouse blood, a validated HPLC-MS/MS method was developed. Chromatographic analysis was performed using C18 (5μm, 150 mm × 4.6 mm). The mobile phase consisted of water containing 0.1% formic acid, acetonitrile, and methanol (35/52/13 v/v/v) at a flow rate and total running time of 0.8 mL/min and 5.50 min, respectively, with an injection volume of 20 µL. 2HF was detected by electrospray ionization in negative mode (ESI-) using multiple reaction monitoring (MRM). The validated bioanalytical method showed satisfactory selectivity without significant interference for the 2HF and IS. In addition, the concentration range between 1 and 250 ng/mL showed good linearity (r = 0.9969). The method showed satisfactory results for the matrix effect. Precision and accuracy intervals varied between 1.89% and 6.76% and 95.27% and 100.77%, respectively, fitting the criteria. No degradation of 2HF in the biological matrix was observed since stability under freezing and thawing conditions, short duration, postprocessing, and long duration showed deviations less than 15%. Once validated, the method was successfully applied in a 2HF oral pharmacokinetic study with mouse blood, and the pharmacokinetic parameters were determined. 2HF demonstrated a Cmax of 185.86 ng/mL, a Tmax of 5 min, and a half-life (T1/2) of 97.52 min.https://www.frontiersin.org/articles/10.3389/fchem.2023.1016193/fullHPLC-MS/MSpharmacokinetics2′-hydroxiflavanoneflavonoidoral treatment
spellingShingle Luiza F. O. Gervazoni
Gabriella Gonçalves-Ozorio
Taiana Ferreira-Paes
Aline C. A. Silva
Gabriel P. E. Silveira
Heliana M. Pereira
Douglas P. Pinto
Edézio F. Cunha-Junior
Elmo E. Almeida-Amaral
Analysis of 2′-hydroxyflavanone (2HF) in mouse whole blood by HPLC–MS/MS for the determination of pharmacokinetic parameters
Frontiers in Chemistry
HPLC-MS/MS
pharmacokinetics
2′-hydroxiflavanone
flavonoid
oral treatment
title Analysis of 2′-hydroxyflavanone (2HF) in mouse whole blood by HPLC–MS/MS for the determination of pharmacokinetic parameters
title_full Analysis of 2′-hydroxyflavanone (2HF) in mouse whole blood by HPLC–MS/MS for the determination of pharmacokinetic parameters
title_fullStr Analysis of 2′-hydroxyflavanone (2HF) in mouse whole blood by HPLC–MS/MS for the determination of pharmacokinetic parameters
title_full_unstemmed Analysis of 2′-hydroxyflavanone (2HF) in mouse whole blood by HPLC–MS/MS for the determination of pharmacokinetic parameters
title_short Analysis of 2′-hydroxyflavanone (2HF) in mouse whole blood by HPLC–MS/MS for the determination of pharmacokinetic parameters
title_sort analysis of 2 hydroxyflavanone 2hf in mouse whole blood by hplc ms ms for the determination of pharmacokinetic parameters
topic HPLC-MS/MS
pharmacokinetics
2′-hydroxiflavanone
flavonoid
oral treatment
url https://www.frontiersin.org/articles/10.3389/fchem.2023.1016193/full
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