Setup and validation of shake-flask procedures for the determinationof partition coefficients (log D) from low drug amounts

Several procedures based on the shake-flask method and designed to require a minimum amount of drug for octanol-water partition coefficient determination have been established and developed. The procedures have been validated by a 28 substance set with a lipophilicity range from -2.0 to 4.5 (logD7.4...

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Autores: Andrés Sanz, Axel, Rosés Pascual, Martí, Ràfols Llach, Clara, Bosch, Elisabeth, Espinosa Ferrer, Sonia, Segarra, Victor, Huerta Castaño, José María
Tipo de documento: artigo
Estado:Versión aceptada para publicación
Data de publicação:2015
País:España
Recursos:Universidad de Barcelona
Repositório:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/143737
Acesso em linha:https://hdl.handle.net/2445/143737
Access Level:Acceso aberto
Palavra-chave:Lipofília
Química farmacèutica
Lipophilicity
Pharmaceutical chemistry
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spelling Setup and validation of shake-flask procedures for the determinationof partition coefficients (log D) from low drug amountsAndrés Sanz, AxelRosés Pascual, MartíRàfols Llach, ClaraBosch, ElisabethEspinosa Ferrer, SoniaSegarra, VictorHuerta Castaño, José MaríaLipofíliaQuímica farmacèuticaLipophilicityPharmaceutical chemistrySeveral procedures based on the shake-flask method and designed to require a minimum amount of drug for octanol-water partition coefficient determination have been established and developed. The procedures have been validated by a 28 substance set with a lipophilicity range from -2.0 to 4.5 (logD7.4). The experimental partition is carried out using aqueous phases buffered with phosphate (pH 7.4) and n-octanol saturated with buffered water and the analysis is performed by liquid chromatography. In order to have accurate results, four procedures and eight different ratios between phase volumes are proposed. Each procedure has been designed and optimized (for partition ratios) for a specific range of drug lipophilicity (low, regular and high lipophilicity) and solubility (high and low aqueous solubility). The procedures have been developed to minimize the measurement in the octanolic phase. Experimental logD7.4 values obtained from different procedures and partition ratios show a standard deviation lower than 0.3 and there is a nice agreement when these values are compared with the reference literature onesElsevier B.V.2015info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/143737Articles publicats en revistes (Enginyeria Química i Química Analítica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.1016/j.ejps.2015.05.008European Journal of Pharmaceutical Sciences, 2015, vol. 76, p. 181-191https://doi.org/10.1016/j.ejps.2015.05.008cc-by-nc-nd (c) Elsevier B.V., 2015http://creativecommons.org/licenses/by-nc-nd/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1437372026-05-27T06:46:51Z
dc.title.none.fl_str_mv Setup and validation of shake-flask procedures for the determinationof partition coefficients (log D) from low drug amounts
title Setup and validation of shake-flask procedures for the determinationof partition coefficients (log D) from low drug amounts
spellingShingle Setup and validation of shake-flask procedures for the determinationof partition coefficients (log D) from low drug amounts
Andrés Sanz, Axel
Lipofília
Química farmacèutica
Lipophilicity
Pharmaceutical chemistry
title_short Setup and validation of shake-flask procedures for the determinationof partition coefficients (log D) from low drug amounts
title_full Setup and validation of shake-flask procedures for the determinationof partition coefficients (log D) from low drug amounts
title_fullStr Setup and validation of shake-flask procedures for the determinationof partition coefficients (log D) from low drug amounts
title_full_unstemmed Setup and validation of shake-flask procedures for the determinationof partition coefficients (log D) from low drug amounts
title_sort Setup and validation of shake-flask procedures for the determinationof partition coefficients (log D) from low drug amounts
dc.creator.none.fl_str_mv Andrés Sanz, Axel
Rosés Pascual, Martí
Ràfols Llach, Clara
Bosch, Elisabeth
Espinosa Ferrer, Sonia
Segarra, Victor
Huerta Castaño, José María
author Andrés Sanz, Axel
author_facet Andrés Sanz, Axel
Rosés Pascual, Martí
Ràfols Llach, Clara
Bosch, Elisabeth
Espinosa Ferrer, Sonia
Segarra, Victor
Huerta Castaño, José María
author_role author
author2 Rosés Pascual, Martí
Ràfols Llach, Clara
Bosch, Elisabeth
Espinosa Ferrer, Sonia
Segarra, Victor
Huerta Castaño, José María
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Lipofília
Química farmacèutica
Lipophilicity
Pharmaceutical chemistry
topic Lipofília
Química farmacèutica
Lipophilicity
Pharmaceutical chemistry
description Several procedures based on the shake-flask method and designed to require a minimum amount of drug for octanol-water partition coefficient determination have been established and developed. The procedures have been validated by a 28 substance set with a lipophilicity range from -2.0 to 4.5 (logD7.4). The experimental partition is carried out using aqueous phases buffered with phosphate (pH 7.4) and n-octanol saturated with buffered water and the analysis is performed by liquid chromatography. In order to have accurate results, four procedures and eight different ratios between phase volumes are proposed. Each procedure has been designed and optimized (for partition ratios) for a specific range of drug lipophilicity (low, regular and high lipophilicity) and solubility (high and low aqueous solubility). The procedures have been developed to minimize the measurement in the octanolic phase. Experimental logD7.4 values obtained from different procedures and partition ratios show a standard deviation lower than 0.3 and there is a nice agreement when these values are compared with the reference literature ones
publishDate 2015
dc.date.none.fl_str_mv 2015
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/143737
url https://hdl.handle.net/2445/143737
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1016/j.ejps.2015.05.008
European Journal of Pharmaceutical Sciences, 2015, vol. 76, p. 181-191
https://doi.org/10.1016/j.ejps.2015.05.008
dc.rights.none.fl_str_mv cc-by-nc-nd (c) Elsevier B.V., 2015
http://creativecommons.org/licenses/by-nc-nd/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by-nc-nd (c) Elsevier B.V., 2015
http://creativecommons.org/licenses/by-nc-nd/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier B.V.
publisher.none.fl_str_mv Elsevier B.V.
dc.source.none.fl_str_mv Articles publicats en revistes (Enginyeria Química i Química Analítica)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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