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Stability evaluation of compounded hydroxyurea 100 mg/mL oral liquids using a novel analytical method involving chemical derivatization

This study assessed the stability of six extemporaneously compounded hydroxyurea oral liquids stored at room temperature. Hydroxyurea oral liquids (100 mg/mL) were prepared using three different mixing methods (mortar, mixer or QuartetRx) from either bulk powder, capsule content, or whole capsules....

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Autores principales: Coache, Daphné, Friciu, Mihaela, Bernine Marcellin, Ruth, Bonnemain, Lola, Viau, Annie, Roullin, V. Gaëlle, Forest, Jean-Marc, Leclair, Grégoire
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231814/
https://www.ncbi.nlm.nih.gov/pubmed/35749410
http://dx.doi.org/10.1371/journal.pone.0270206
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author Coache, Daphné
Friciu, Mihaela
Bernine Marcellin, Ruth
Bonnemain, Lola
Viau, Annie
Roullin, V. Gaëlle
Forest, Jean-Marc
Leclair, Grégoire
author_facet Coache, Daphné
Friciu, Mihaela
Bernine Marcellin, Ruth
Bonnemain, Lola
Viau, Annie
Roullin, V. Gaëlle
Forest, Jean-Marc
Leclair, Grégoire
author_sort Coache, Daphné
collection PubMed
description This study assessed the stability of six extemporaneously compounded hydroxyurea oral liquids stored at room temperature. Hydroxyurea oral liquids (100 mg/mL) were prepared using three different mixing methods (mortar, mixer or QuartetRx) from either bulk powder, capsule content, or whole capsules. Two brands of capsules were tested in this study. All formulations were stored at room temperature (25°C / 60% RH) in amber plastic bottles for 90 days and amber plastic syringes for 14 days. Physical stability was assessed visually, while chemical stability was evaluated using a stability-indicating high-performance liquid chromatography method. Chemical derivatization with xanthydrol allowed the retention of hydroxyurea on a reverse-phase column. At least 93.9% and 97.0% of the initial concentration of hydroxyurea remained after 90 days in bottles and 14 days in syringes, respectively. There were no visual changes in formulations over the study period. Changes in pH up to 1.6 units were observed after 90 days of storage and were explained most likely by an ammonium generating degradation pathway. Ammonium was quantified and remained within safe levels in each HU 100 mg/mL oral preparations. Hydroxyurea oral liquids were all stable for 90 days in amber plastic bottles and 14 days in amber plastic syringes.
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spelling pubmed-92318142022-06-25 Stability evaluation of compounded hydroxyurea 100 mg/mL oral liquids using a novel analytical method involving chemical derivatization Coache, Daphné Friciu, Mihaela Bernine Marcellin, Ruth Bonnemain, Lola Viau, Annie Roullin, V. Gaëlle Forest, Jean-Marc Leclair, Grégoire PLoS One Research Article This study assessed the stability of six extemporaneously compounded hydroxyurea oral liquids stored at room temperature. Hydroxyurea oral liquids (100 mg/mL) were prepared using three different mixing methods (mortar, mixer or QuartetRx) from either bulk powder, capsule content, or whole capsules. Two brands of capsules were tested in this study. All formulations were stored at room temperature (25°C / 60% RH) in amber plastic bottles for 90 days and amber plastic syringes for 14 days. Physical stability was assessed visually, while chemical stability was evaluated using a stability-indicating high-performance liquid chromatography method. Chemical derivatization with xanthydrol allowed the retention of hydroxyurea on a reverse-phase column. At least 93.9% and 97.0% of the initial concentration of hydroxyurea remained after 90 days in bottles and 14 days in syringes, respectively. There were no visual changes in formulations over the study period. Changes in pH up to 1.6 units were observed after 90 days of storage and were explained most likely by an ammonium generating degradation pathway. Ammonium was quantified and remained within safe levels in each HU 100 mg/mL oral preparations. Hydroxyurea oral liquids were all stable for 90 days in amber plastic bottles and 14 days in amber plastic syringes. Public Library of Science 2022-06-24 /pmc/articles/PMC9231814/ /pubmed/35749410 http://dx.doi.org/10.1371/journal.pone.0270206 Text en © 2022 Coache et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Coache, Daphné
Friciu, Mihaela
Bernine Marcellin, Ruth
Bonnemain, Lola
Viau, Annie
Roullin, V. Gaëlle
Forest, Jean-Marc
Leclair, Grégoire
Stability evaluation of compounded hydroxyurea 100 mg/mL oral liquids using a novel analytical method involving chemical derivatization
title Stability evaluation of compounded hydroxyurea 100 mg/mL oral liquids using a novel analytical method involving chemical derivatization
title_full Stability evaluation of compounded hydroxyurea 100 mg/mL oral liquids using a novel analytical method involving chemical derivatization
title_fullStr Stability evaluation of compounded hydroxyurea 100 mg/mL oral liquids using a novel analytical method involving chemical derivatization
title_full_unstemmed Stability evaluation of compounded hydroxyurea 100 mg/mL oral liquids using a novel analytical method involving chemical derivatization
title_short Stability evaluation of compounded hydroxyurea 100 mg/mL oral liquids using a novel analytical method involving chemical derivatization
title_sort stability evaluation of compounded hydroxyurea 100 mg/ml oral liquids using a novel analytical method involving chemical derivatization
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231814/
https://www.ncbi.nlm.nih.gov/pubmed/35749410
http://dx.doi.org/10.1371/journal.pone.0270206
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