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Development and Validation of a Novel LC-MS/MS Method for a TDM-Guided Personalization of HSCT Conditioning with High-Dose Busulfan in Children

Personalization of busulfan (Bu) exposure via therapeutic drug monitoring (TDM) is recommended for patients treated with high-dose conditioning regimens. Several laboratories’ developed methods are available in the literature with a lack of standardization. The aim of this study is to develop a new...

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Autores principales: Cafaro, Alessia, Pigliasco, Federica, Baiardi, Giammarco, Barco, Sebastiano, Stella, Manuela, Bandettini, Roberto, Mattioli, Francesca, Faraci, Maura, Cangemi, Giuliana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953620/
https://www.ncbi.nlm.nih.gov/pubmed/36831066
http://dx.doi.org/10.3390/biomedicines11020530
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author Cafaro, Alessia
Pigliasco, Federica
Baiardi, Giammarco
Barco, Sebastiano
Stella, Manuela
Bandettini, Roberto
Mattioli, Francesca
Faraci, Maura
Cangemi, Giuliana
author_facet Cafaro, Alessia
Pigliasco, Federica
Baiardi, Giammarco
Barco, Sebastiano
Stella, Manuela
Bandettini, Roberto
Mattioli, Francesca
Faraci, Maura
Cangemi, Giuliana
author_sort Cafaro, Alessia
collection PubMed
description Personalization of busulfan (Bu) exposure via therapeutic drug monitoring (TDM) is recommended for patients treated with high-dose conditioning regimens. Several laboratories’ developed methods are available in the literature with a lack of standardization. The aim of this study is to develop a new standardized LC-MS/MS method and validate it according to the international ICH M10 (EMA) guidelines. Our method is based on rapid protein precipitation from 50 µL plasma followed by separation on a reversed-phase C-18 UHPLC column after the addition of deuterated internal standard and has been tested on real samples from pediatric patients treated with myeloablative conditioning regimens, including Bu, before autologous or allogeneic hematopoietic stem cell transplantation (HSCT). The validated LC-MS/MS method is linear over wide concentration ranges (125–2000 ng/mL), accurate, and reproducible in the absence of matrix effects, allowing for the specific and rapid quantification of Bu and allowing next-dose recommendations to be made in a timely fashion to answer clinicians’ needs. Given the lack of data on the stability of Bu in real clinical samples, stability was assessed both on quality controls and on real samples to set up a robust protocol in real-life conditions. This novel LC-MS/MS method is suitable for application to the TDM-guided personalization of conditioning treatments with high-dose busulfan in pediatric patients undergoing HSCT.
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spelling pubmed-99536202023-02-25 Development and Validation of a Novel LC-MS/MS Method for a TDM-Guided Personalization of HSCT Conditioning with High-Dose Busulfan in Children Cafaro, Alessia Pigliasco, Federica Baiardi, Giammarco Barco, Sebastiano Stella, Manuela Bandettini, Roberto Mattioli, Francesca Faraci, Maura Cangemi, Giuliana Biomedicines Article Personalization of busulfan (Bu) exposure via therapeutic drug monitoring (TDM) is recommended for patients treated with high-dose conditioning regimens. Several laboratories’ developed methods are available in the literature with a lack of standardization. The aim of this study is to develop a new standardized LC-MS/MS method and validate it according to the international ICH M10 (EMA) guidelines. Our method is based on rapid protein precipitation from 50 µL plasma followed by separation on a reversed-phase C-18 UHPLC column after the addition of deuterated internal standard and has been tested on real samples from pediatric patients treated with myeloablative conditioning regimens, including Bu, before autologous or allogeneic hematopoietic stem cell transplantation (HSCT). The validated LC-MS/MS method is linear over wide concentration ranges (125–2000 ng/mL), accurate, and reproducible in the absence of matrix effects, allowing for the specific and rapid quantification of Bu and allowing next-dose recommendations to be made in a timely fashion to answer clinicians’ needs. Given the lack of data on the stability of Bu in real clinical samples, stability was assessed both on quality controls and on real samples to set up a robust protocol in real-life conditions. This novel LC-MS/MS method is suitable for application to the TDM-guided personalization of conditioning treatments with high-dose busulfan in pediatric patients undergoing HSCT. MDPI 2023-02-11 /pmc/articles/PMC9953620/ /pubmed/36831066 http://dx.doi.org/10.3390/biomedicines11020530 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cafaro, Alessia
Pigliasco, Federica
Baiardi, Giammarco
Barco, Sebastiano
Stella, Manuela
Bandettini, Roberto
Mattioli, Francesca
Faraci, Maura
Cangemi, Giuliana
Development and Validation of a Novel LC-MS/MS Method for a TDM-Guided Personalization of HSCT Conditioning with High-Dose Busulfan in Children
title Development and Validation of a Novel LC-MS/MS Method for a TDM-Guided Personalization of HSCT Conditioning with High-Dose Busulfan in Children
title_full Development and Validation of a Novel LC-MS/MS Method for a TDM-Guided Personalization of HSCT Conditioning with High-Dose Busulfan in Children
title_fullStr Development and Validation of a Novel LC-MS/MS Method for a TDM-Guided Personalization of HSCT Conditioning with High-Dose Busulfan in Children
title_full_unstemmed Development and Validation of a Novel LC-MS/MS Method for a TDM-Guided Personalization of HSCT Conditioning with High-Dose Busulfan in Children
title_short Development and Validation of a Novel LC-MS/MS Method for a TDM-Guided Personalization of HSCT Conditioning with High-Dose Busulfan in Children
title_sort development and validation of a novel lc-ms/ms method for a tdm-guided personalization of hsct conditioning with high-dose busulfan in children
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9953620/
https://www.ncbi.nlm.nih.gov/pubmed/36831066
http://dx.doi.org/10.3390/biomedicines11020530
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