An Ultrafast Ultrahigh-Performance Liquid Chromatography Coupled With Tandem Mass Spectrometry Method for Cannabidiol Monitoring in Pediatric Refractory Epilepsy

Autores
Pérez Montilla, Carlos Alberto; Schaiquevich, Paula Susana; Caceres Guido, Paulo Arturo; Caraballo, Roberto Horacio; Reyes Valenzuela, Gabriela; Cruz, Cintia V.; García Bournissen, Facundo
Año de publicación
2021
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Cannabidiol (CBD) is a nonpsychoactive natural product that has been increasingly used as a promising new drug for the management of neurological conditions such as refractory epilepsy. Development of rapid and sensitive methods to quantitate CBD is essential to evaluate its pharmacokinetics in humans, particularly in children. The objective of this work was to develop and validate an ultrafast ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) method for CBD quantitation that is capable of detecting major CBD and tetrahydrocannabinol (THC) metabolites in the plasma of pediatric refractory epilepsy patients.Methods: Eight-point CBD calibration curves were prepared using 60 µL of plasma from healthy volunteers. Samples were analyzed in a Shimadzu Nexera X2 UHPLC system, which was coupled to a Sciex QTRAP 6500 mass spectrometer. Chromatography was optimized in acetonitrile (ACN)/water with a 70%-90% gradient of ACN in 2 minutes. Multiple reaction monitoring transitions of major CBD and THC metabolites were optimized in patient plasma.Results: The optimized UHPLC-MS/MS method was validated for the linear range (1-300 ng/mL) of CBD (r2 = 0.996). The limit of quantification and limit of detection were 0.26 and 0.86 ng/mL, respectively. Accuracy and precision met the acceptable validation limits. CBD recovery and matrix effects were 83.9 ± 13.9% and 117.4 ± 4.5%, respectively. The method was successfully applied to quantify CBD and detect the major CBD and THC metabolites in clinical samples. 7-COOH-CBD was the most intensely detected metabolite followed by glucuronide conjugates.Conclusions: A simple and sensitive method for rapidly monitoring CBD and identifying relevant metabolites was developed. Its applicability in samples from children treated for epilepsy was demonstrated, making it an excellent alternative for performing pharmacokinetic studies.
Fil: Pérez Montilla, Carlos Alberto. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina
Fil: Schaiquevich, Paula Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Caceres Guido, Paulo Arturo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Caraballo, Roberto Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Reyes Valenzuela, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Cruz, Cintia V.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina
Fil: García Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Western University; Canadá
Materia
Cannabidiol
HPLC
Refractory epilepsia
Monitoring
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:11336/162942
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/162942
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling An Ultrafast Ultrahigh-Performance Liquid Chromatography Coupled With Tandem Mass Spectrometry Method for Cannabidiol Monitoring in Pediatric Refractory EpilepsyPérez Montilla, Carlos AlbertoSchaiquevich, Paula SusanaCaceres Guido, Paulo ArturoCaraballo, Roberto HoracioReyes Valenzuela, GabrielaCruz, Cintia V.García Bournissen, FacundoCannabidiolHPLCRefractory epilepsiaMonitoringhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: Cannabidiol (CBD) is a nonpsychoactive natural product that has been increasingly used as a promising new drug for the management of neurological conditions such as refractory epilepsy. Development of rapid and sensitive methods to quantitate CBD is essential to evaluate its pharmacokinetics in humans, particularly in children. The objective of this work was to develop and validate an ultrafast ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) method for CBD quantitation that is capable of detecting major CBD and tetrahydrocannabinol (THC) metabolites in the plasma of pediatric refractory epilepsy patients.Methods: Eight-point CBD calibration curves were prepared using 60 µL of plasma from healthy volunteers. Samples were analyzed in a Shimadzu Nexera X2 UHPLC system, which was coupled to a Sciex QTRAP 6500 mass spectrometer. Chromatography was optimized in acetonitrile (ACN)/water with a 70%-90% gradient of ACN in 2 minutes. Multiple reaction monitoring transitions of major CBD and THC metabolites were optimized in patient plasma.Results: The optimized UHPLC-MS/MS method was validated for the linear range (1-300 ng/mL) of CBD (r2 = 0.996). The limit of quantification and limit of detection were 0.26 and 0.86 ng/mL, respectively. Accuracy and precision met the acceptable validation limits. CBD recovery and matrix effects were 83.9 ± 13.9% and 117.4 ± 4.5%, respectively. The method was successfully applied to quantify CBD and detect the major CBD and THC metabolites in clinical samples. 7-COOH-CBD was the most intensely detected metabolite followed by glucuronide conjugates.Conclusions: A simple and sensitive method for rapidly monitoring CBD and identifying relevant metabolites was developed. Its applicability in samples from children treated for epilepsy was demonstrated, making it an excellent alternative for performing pharmacokinetic studies.Fil: Pérez Montilla, Carlos Alberto. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Schaiquevich, Paula Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Caceres Guido, Paulo Arturo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Caraballo, Roberto Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Reyes Valenzuela, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; ArgentinaFil: Cruz, Cintia V.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; ArgentinaFil: García Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Western University; CanadáLippincott Williams2021-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/162942Pérez Montilla, Carlos Alberto; Schaiquevich, Paula Susana; Caceres Guido, Paulo Arturo; Caraballo, Roberto Horacio; Reyes Valenzuela, Gabriela; et al.; An Ultrafast Ultrahigh-Performance Liquid Chromatography Coupled With Tandem Mass Spectrometry Method for Cannabidiol Monitoring in Pediatric Refractory Epilepsy; Lippincott Williams; Therapeutic Drug Monitoring; 43; 5; 10-2021; 1-260163-4356CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1097/FTD.0000000000000846info:eu-repo/semantics/altIdentifier/url/https://journals.lww.com/drug-monitoring/Abstract/2021/10000/An_Ultrafast_Ultrahigh_Performance_Liquid.18.aspxinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T10:50:29Zoai:ri.conicet.gov.ar:11336/162942instacron: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:34982025-09-17 10:50:29.448CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv An Ultrafast Ultrahigh-Performance Liquid Chromatography Coupled With Tandem Mass Spectrometry Method for Cannabidiol Monitoring in Pediatric Refractory Epilepsy
title An Ultrafast Ultrahigh-Performance Liquid Chromatography Coupled With Tandem Mass Spectrometry Method for Cannabidiol Monitoring in Pediatric Refractory Epilepsy
spellingShingle An Ultrafast Ultrahigh-Performance Liquid Chromatography Coupled With Tandem Mass Spectrometry Method for Cannabidiol Monitoring in Pediatric Refractory Epilepsy
Pérez Montilla, Carlos Alberto
Cannabidiol
HPLC
Refractory epilepsia
Monitoring
title_short An Ultrafast Ultrahigh-Performance Liquid Chromatography Coupled With Tandem Mass Spectrometry Method for Cannabidiol Monitoring in Pediatric Refractory Epilepsy
title_full An Ultrafast Ultrahigh-Performance Liquid Chromatography Coupled With Tandem Mass Spectrometry Method for Cannabidiol Monitoring in Pediatric Refractory Epilepsy
title_fullStr An Ultrafast Ultrahigh-Performance Liquid Chromatography Coupled With Tandem Mass Spectrometry Method for Cannabidiol Monitoring in Pediatric Refractory Epilepsy
title_full_unstemmed An Ultrafast Ultrahigh-Performance Liquid Chromatography Coupled With Tandem Mass Spectrometry Method for Cannabidiol Monitoring in Pediatric Refractory Epilepsy
title_sort An Ultrafast Ultrahigh-Performance Liquid Chromatography Coupled With Tandem Mass Spectrometry Method for Cannabidiol Monitoring in Pediatric Refractory Epilepsy
dc.creator.none.fl_str_mv Pérez Montilla, Carlos Alberto
Schaiquevich, Paula Susana
Caceres Guido, Paulo Arturo
Caraballo, Roberto Horacio
Reyes Valenzuela, Gabriela
Cruz, Cintia V.
García Bournissen, Facundo
author Pérez Montilla, Carlos Alberto
author_facet Pérez Montilla, Carlos Alberto
Schaiquevich, Paula Susana
Caceres Guido, Paulo Arturo
Caraballo, Roberto Horacio
Reyes Valenzuela, Gabriela
Cruz, Cintia V.
García Bournissen, Facundo
author_role author
author2 Schaiquevich, Paula Susana
Caceres Guido, Paulo Arturo
Caraballo, Roberto Horacio
Reyes Valenzuela, Gabriela
Cruz, Cintia V.
García Bournissen, Facundo
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Cannabidiol
HPLC
Refractory epilepsia
Monitoring
topic Cannabidiol
HPLC
Refractory epilepsia
Monitoring
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Cannabidiol (CBD) is a nonpsychoactive natural product that has been increasingly used as a promising new drug for the management of neurological conditions such as refractory epilepsy. Development of rapid and sensitive methods to quantitate CBD is essential to evaluate its pharmacokinetics in humans, particularly in children. The objective of this work was to develop and validate an ultrafast ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) method for CBD quantitation that is capable of detecting major CBD and tetrahydrocannabinol (THC) metabolites in the plasma of pediatric refractory epilepsy patients.Methods: Eight-point CBD calibration curves were prepared using 60 µL of plasma from healthy volunteers. Samples were analyzed in a Shimadzu Nexera X2 UHPLC system, which was coupled to a Sciex QTRAP 6500 mass spectrometer. Chromatography was optimized in acetonitrile (ACN)/water with a 70%-90% gradient of ACN in 2 minutes. Multiple reaction monitoring transitions of major CBD and THC metabolites were optimized in patient plasma.Results: The optimized UHPLC-MS/MS method was validated for the linear range (1-300 ng/mL) of CBD (r2 = 0.996). The limit of quantification and limit of detection were 0.26 and 0.86 ng/mL, respectively. Accuracy and precision met the acceptable validation limits. CBD recovery and matrix effects were 83.9 ± 13.9% and 117.4 ± 4.5%, respectively. The method was successfully applied to quantify CBD and detect the major CBD and THC metabolites in clinical samples. 7-COOH-CBD was the most intensely detected metabolite followed by glucuronide conjugates.Conclusions: A simple and sensitive method for rapidly monitoring CBD and identifying relevant metabolites was developed. Its applicability in samples from children treated for epilepsy was demonstrated, making it an excellent alternative for performing pharmacokinetic studies.
Fil: Pérez Montilla, Carlos Alberto. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina
Fil: Schaiquevich, Paula Susana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Caceres Guido, Paulo Arturo. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Caraballo, Roberto Horacio. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Reyes Valenzuela, Gabriela. Gobierno de la Ciudad de Buenos Aires. Hospital de Pediatría "Juan P. Garrahan"; Argentina
Fil: Cruz, Cintia V.. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Farmacología; Argentina
Fil: García Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina. Western University; Canadá
description Background: Cannabidiol (CBD) is a nonpsychoactive natural product that has been increasingly used as a promising new drug for the management of neurological conditions such as refractory epilepsy. Development of rapid and sensitive methods to quantitate CBD is essential to evaluate its pharmacokinetics in humans, particularly in children. The objective of this work was to develop and validate an ultrafast ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) method for CBD quantitation that is capable of detecting major CBD and tetrahydrocannabinol (THC) metabolites in the plasma of pediatric refractory epilepsy patients.Methods: Eight-point CBD calibration curves were prepared using 60 µL of plasma from healthy volunteers. Samples were analyzed in a Shimadzu Nexera X2 UHPLC system, which was coupled to a Sciex QTRAP 6500 mass spectrometer. Chromatography was optimized in acetonitrile (ACN)/water with a 70%-90% gradient of ACN in 2 minutes. Multiple reaction monitoring transitions of major CBD and THC metabolites were optimized in patient plasma.Results: The optimized UHPLC-MS/MS method was validated for the linear range (1-300 ng/mL) of CBD (r2 = 0.996). The limit of quantification and limit of detection were 0.26 and 0.86 ng/mL, respectively. Accuracy and precision met the acceptable validation limits. CBD recovery and matrix effects were 83.9 ± 13.9% and 117.4 ± 4.5%, respectively. The method was successfully applied to quantify CBD and detect the major CBD and THC metabolites in clinical samples. 7-COOH-CBD was the most intensely detected metabolite followed by glucuronide conjugates.Conclusions: A simple and sensitive method for rapidly monitoring CBD and identifying relevant metabolites was developed. Its applicability in samples from children treated for epilepsy was demonstrated, making it an excellent alternative for performing pharmacokinetic studies.
publishDate 2021
dc.date.none.fl_str_mv 2021-10
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/11336/162942
Pérez Montilla, Carlos Alberto; Schaiquevich, Paula Susana; Caceres Guido, Paulo Arturo; Caraballo, Roberto Horacio; Reyes Valenzuela, Gabriela; et al.; An Ultrafast Ultrahigh-Performance Liquid Chromatography Coupled With Tandem Mass Spectrometry Method for Cannabidiol Monitoring in Pediatric Refractory Epilepsy; Lippincott Williams; Therapeutic Drug Monitoring; 43; 5; 10-2021; 1-26
0163-4356
CONICET Digital
CONICET
url http://hdl.handle.net/11336/162942
identifier_str_mv Pérez Montilla, Carlos Alberto; Schaiquevich, Paula Susana; Caceres Guido, Paulo Arturo; Caraballo, Roberto Horacio; Reyes Valenzuela, Gabriela; et al.; An Ultrafast Ultrahigh-Performance Liquid Chromatography Coupled With Tandem Mass Spectrometry Method for Cannabidiol Monitoring in Pediatric Refractory Epilepsy; Lippincott Williams; Therapeutic Drug Monitoring; 43; 5; 10-2021; 1-26
0163-4356
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1097/FTD.0000000000000846
info:eu-repo/semantics/altIdentifier/url/https://journals.lww.com/drug-monitoring/Abstract/2021/10000/An_Ultrafast_Ultrahigh_Performance_Liquid.18.aspx
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
application/pdf
dc.publisher.none.fl_str_mv Lippincott Williams
publisher.none.fl_str_mv Lippincott Williams
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 13.001348

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