Saliva as a noninvasive biological sample to compare bioavailability of phenytoin formulations by LC-MS/MS

Autores
Baldo, Matias Nicolas; Hunzicker, Gabriel Alejandro; Altamirano, Jorgelina Cecilia; Murguia, Marcelo Cesar; Hein, Gustavo Juan
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The use of noninvasive biological samples such as saliva, it is of great interest for therapeutic drug monitoring (TDM), including the anticonvulsants Phenytoin (PHT). A simple analytical methodology by liquid chromatography-tandem mass spectrometry was developed and validated to carry out a relative comparative bioavailability (RBA) study of two PHT formulations in human plasma and saliva and the subsequent correlation between both matrixes. A single-dose, randomized-sequence, open-label, two-way crossover study, was conducted in 24 healthy Latin American male volunteers. The bioequivalence of 200 mg PHT tablet was evaluated using plasma and saliva to determine Cmax, Tmax, AUC0-t and AUC0-∞. Figures of merit of the proposed methodology were as follows: linear ranges of 40-5055 ng/mL and 5-1340 ng/mL for plasma and saliva, respectively, with a correlation coefficient of (r)>0.999. The LOD and LOQ were 15 ng/mL -40ng/mL for plasma and 1.5 ng/mL – 5.0 ng/mL for saliva. Accuracy, precision (as %CV) and recovery were accepted according the bioequivalence criteria. Stability showed %bias<15%. The PHT saliva/PHT plasma ratios for all parameters were: 5.4, 2.2, 1.4 for Cmax, and 1.7, 1.2, 1.1 for AUC. Plasma and saliva results were correlated (R=0.9889 and R=0.9947 for Reference and Test, respectively). Saliva not only is a suitable matrix for RBA studies and TDM, but also a more convenient tool since it provides analogous information with mayor analytical, ethical, and biosafety advantages. However, an additional pre-study of product dissolution in oral cavity is suggested before carrying out complete RBA studies for prompt-release drugs
Fil: Baldo, Matias Nicolas. Dominguez Lab; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina
Fil: Hunzicker, Gabriel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dominguez Lab; Argentina
Fil: Altamirano, Jorgelina Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; Argentina
Fil: Murguia, Marcelo Cesar. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Hein, Gustavo Juan. Dominguez Lab; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina
Materia
Phenytoin
Saliva
Bioequivalence
Lc-Ms/Ms
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/39591
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Saliva as a noninvasive biological sample to compare bioavailability of phenytoin formulations by LC-MS/MSBaldo, Matias NicolasHunzicker, Gabriel AlejandroAltamirano, Jorgelina CeciliaMurguia, Marcelo CesarHein, Gustavo JuanPhenytoinSalivaBioequivalenceLc-Ms/Mshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The use of noninvasive biological samples such as saliva, it is of great interest for therapeutic drug monitoring (TDM), including the anticonvulsants Phenytoin (PHT). A simple analytical methodology by liquid chromatography-tandem mass spectrometry was developed and validated to carry out a relative comparative bioavailability (RBA) study of two PHT formulations in human plasma and saliva and the subsequent correlation between both matrixes. A single-dose, randomized-sequence, open-label, two-way crossover study, was conducted in 24 healthy Latin American male volunteers. The bioequivalence of 200 mg PHT tablet was evaluated using plasma and saliva to determine Cmax, Tmax, AUC0-t and AUC0-∞. Figures of merit of the proposed methodology were as follows: linear ranges of 40-5055 ng/mL and 5-1340 ng/mL for plasma and saliva, respectively, with a correlation coefficient of (r)>0.999. The LOD and LOQ were 15 ng/mL -40ng/mL for plasma and 1.5 ng/mL – 5.0 ng/mL for saliva. Accuracy, precision (as %CV) and recovery were accepted according the bioequivalence criteria. Stability showed %bias<15%. The PHT saliva/PHT plasma ratios for all parameters were: 5.4, 2.2, 1.4 for Cmax, and 1.7, 1.2, 1.1 for AUC. Plasma and saliva results were correlated (R=0.9889 and R=0.9947 for Reference and Test, respectively). Saliva not only is a suitable matrix for RBA studies and TDM, but also a more convenient tool since it provides analogous information with mayor analytical, ethical, and biosafety advantages. However, an additional pre-study of product dissolution in oral cavity is suggested before carrying out complete RBA studies for prompt-release drugsFil: Baldo, Matias Nicolas. Dominguez Lab; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaFil: Hunzicker, Gabriel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dominguez Lab; ArgentinaFil: Altamirano, Jorgelina Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Murguia, Marcelo Cesar. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Hein, Gustavo Juan. Dominguez Lab; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; ArgentinaElsevier2015-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/39591Baldo, Matias Nicolas; Hunzicker, Gabriel Alejandro; Altamirano, Jorgelina Cecilia; Murguia, Marcelo Cesar; Hein, Gustavo Juan; Saliva as a noninvasive biological sample to compare bioavailability of phenytoin formulations by LC-MS/MS; Elsevier; International Journal of Pharmaceutical Sciences and Research; 6; 9; 9-2015; 3752-37602320-51480975-8232CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.13040/IJPSR.0975-8232.6(9).3752-60info:eu-repo/semantics/altIdentifier/url/http://ijpsr.com/bft-article/saliva-as-a-noninvasive-biological-sample-to-compare-bioavailability-of-phenytoin-formulations-by-lc-msms/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:46:30Zoai:ri.conicet.gov.ar:11336/39591instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:46:30.347CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Saliva as a noninvasive biological sample to compare bioavailability of phenytoin formulations by LC-MS/MS
title Saliva as a noninvasive biological sample to compare bioavailability of phenytoin formulations by LC-MS/MS
spellingShingle Saliva as a noninvasive biological sample to compare bioavailability of phenytoin formulations by LC-MS/MS
Baldo, Matias Nicolas
Phenytoin
Saliva
Bioequivalence
Lc-Ms/Ms
title_short Saliva as a noninvasive biological sample to compare bioavailability of phenytoin formulations by LC-MS/MS
title_full Saliva as a noninvasive biological sample to compare bioavailability of phenytoin formulations by LC-MS/MS
title_fullStr Saliva as a noninvasive biological sample to compare bioavailability of phenytoin formulations by LC-MS/MS
title_full_unstemmed Saliva as a noninvasive biological sample to compare bioavailability of phenytoin formulations by LC-MS/MS
title_sort Saliva as a noninvasive biological sample to compare bioavailability of phenytoin formulations by LC-MS/MS
dc.creator.none.fl_str_mv Baldo, Matias Nicolas
Hunzicker, Gabriel Alejandro
Altamirano, Jorgelina Cecilia
Murguia, Marcelo Cesar
Hein, Gustavo Juan
author Baldo, Matias Nicolas
author_facet Baldo, Matias Nicolas
Hunzicker, Gabriel Alejandro
Altamirano, Jorgelina Cecilia
Murguia, Marcelo Cesar
Hein, Gustavo Juan
author_role author
author2 Hunzicker, Gabriel Alejandro
Altamirano, Jorgelina Cecilia
Murguia, Marcelo Cesar
Hein, Gustavo Juan
author2_role author
author
author
author
dc.subject.none.fl_str_mv Phenytoin
Saliva
Bioequivalence
Lc-Ms/Ms
topic Phenytoin
Saliva
Bioequivalence
Lc-Ms/Ms
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The use of noninvasive biological samples such as saliva, it is of great interest for therapeutic drug monitoring (TDM), including the anticonvulsants Phenytoin (PHT). A simple analytical methodology by liquid chromatography-tandem mass spectrometry was developed and validated to carry out a relative comparative bioavailability (RBA) study of two PHT formulations in human plasma and saliva and the subsequent correlation between both matrixes. A single-dose, randomized-sequence, open-label, two-way crossover study, was conducted in 24 healthy Latin American male volunteers. The bioequivalence of 200 mg PHT tablet was evaluated using plasma and saliva to determine Cmax, Tmax, AUC0-t and AUC0-∞. Figures of merit of the proposed methodology were as follows: linear ranges of 40-5055 ng/mL and 5-1340 ng/mL for plasma and saliva, respectively, with a correlation coefficient of (r)>0.999. The LOD and LOQ were 15 ng/mL -40ng/mL for plasma and 1.5 ng/mL – 5.0 ng/mL for saliva. Accuracy, precision (as %CV) and recovery were accepted according the bioequivalence criteria. Stability showed %bias<15%. The PHT saliva/PHT plasma ratios for all parameters were: 5.4, 2.2, 1.4 for Cmax, and 1.7, 1.2, 1.1 for AUC. Plasma and saliva results were correlated (R=0.9889 and R=0.9947 for Reference and Test, respectively). Saliva not only is a suitable matrix for RBA studies and TDM, but also a more convenient tool since it provides analogous information with mayor analytical, ethical, and biosafety advantages. However, an additional pre-study of product dissolution in oral cavity is suggested before carrying out complete RBA studies for prompt-release drugs
Fil: Baldo, Matias Nicolas. Dominguez Lab; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina
Fil: Hunzicker, Gabriel Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dominguez Lab; Argentina
Fil: Altamirano, Jorgelina Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; Argentina
Fil: Murguia, Marcelo Cesar. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Hein, Gustavo Juan. Dominguez Lab; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentina
description The use of noninvasive biological samples such as saliva, it is of great interest for therapeutic drug monitoring (TDM), including the anticonvulsants Phenytoin (PHT). A simple analytical methodology by liquid chromatography-tandem mass spectrometry was developed and validated to carry out a relative comparative bioavailability (RBA) study of two PHT formulations in human plasma and saliva and the subsequent correlation between both matrixes. A single-dose, randomized-sequence, open-label, two-way crossover study, was conducted in 24 healthy Latin American male volunteers. The bioequivalence of 200 mg PHT tablet was evaluated using plasma and saliva to determine Cmax, Tmax, AUC0-t and AUC0-∞. Figures of merit of the proposed methodology were as follows: linear ranges of 40-5055 ng/mL and 5-1340 ng/mL for plasma and saliva, respectively, with a correlation coefficient of (r)>0.999. The LOD and LOQ were 15 ng/mL -40ng/mL for plasma and 1.5 ng/mL – 5.0 ng/mL for saliva. Accuracy, precision (as %CV) and recovery were accepted according the bioequivalence criteria. Stability showed %bias<15%. The PHT saliva/PHT plasma ratios for all parameters were: 5.4, 2.2, 1.4 for Cmax, and 1.7, 1.2, 1.1 for AUC. Plasma and saliva results were correlated (R=0.9889 and R=0.9947 for Reference and Test, respectively). Saliva not only is a suitable matrix for RBA studies and TDM, but also a more convenient tool since it provides analogous information with mayor analytical, ethical, and biosafety advantages. However, an additional pre-study of product dissolution in oral cavity is suggested before carrying out complete RBA studies for prompt-release drugs
publishDate 2015
dc.date.none.fl_str_mv 2015-09
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/39591
Baldo, Matias Nicolas; Hunzicker, Gabriel Alejandro; Altamirano, Jorgelina Cecilia; Murguia, Marcelo Cesar; Hein, Gustavo Juan; Saliva as a noninvasive biological sample to compare bioavailability of phenytoin formulations by LC-MS/MS; Elsevier; International Journal of Pharmaceutical Sciences and Research; 6; 9; 9-2015; 3752-3760
2320-5148
0975-8232
CONICET Digital
CONICET
url http://hdl.handle.net/11336/39591
identifier_str_mv Baldo, Matias Nicolas; Hunzicker, Gabriel Alejandro; Altamirano, Jorgelina Cecilia; Murguia, Marcelo Cesar; Hein, Gustavo Juan; Saliva as a noninvasive biological sample to compare bioavailability of phenytoin formulations by LC-MS/MS; Elsevier; International Journal of Pharmaceutical Sciences and Research; 6; 9; 9-2015; 3752-3760
2320-5148
0975-8232
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.13040/IJPSR.0975-8232.6(9).3752-60
info:eu-repo/semantics/altIdentifier/url/http://ijpsr.com/bft-article/saliva-as-a-noninvasive-biological-sample-to-compare-bioavailability-of-phenytoin-formulations-by-lc-msms/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.13397

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