Validated Modernized Assay for Foscarnet in Pharmaceutical Formulations Using Suppressed Ion Chromatography Developed through a Quality by Design Approach

Inspired by the United States Pharmacopoeia (USP) “monograph modernization” initiative, we developed and validated an assay for foscarnet sodium injection solution (“foscavir”), following quality by design (QbD) principles, incorporating design of experiments (DoE) and multivariate data analysis to...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ngoc Phuoc Dinh, Adel Shamshir, Gjani Hulaj, Tobias Jonsson
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	design of experiments foscarnet method development monograph modernization pharmaceutical quality control suppressed ion chromatography Physics QC1-999 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/0422a0794f784914bec856f13daacb59
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:0422a0794f784914bec856f13daacb59
record_format	dspace
spelling	oai:doaj.org-article:0422a0794f784914bec856f13daacb592021-11-25T18:59:23ZValidated Modernized Assay for Foscarnet in Pharmaceutical Formulations Using Suppressed Ion Chromatography Developed through a Quality by Design Approach10.3390/separations81102092297-8739https://doaj.org/article/0422a0794f784914bec856f13daacb592021-11-01T00:00:00Zhttps://www.mdpi.com/2297-8739/8/11/209https://doaj.org/toc/2297-8739Inspired by the United States Pharmacopoeia (USP) “monograph modernization” initiative, we developed and validated an assay for foscarnet sodium injection solution (“foscavir”), following quality by design (QbD) principles, incorporating design of experiments (DoE) and multivariate data analysis to establish the design space and robust setpoint of the method. The resulting analytical procedure was based on ion chromatography (IC) with suppressed conductivity detection, employing an isocratic carbonate–bicarbonate eluent system. The assay was successfully validated at the robust setpoint conditions, according to the guidelines established by the International Council for Harmonization (ICH). The linear range stretched at least from 5 to 100 mg/L with high repeatability (relative standard deviation, RSD ≤ 0.3%) both at the target concentration (60 mg/L) and at 50% and 150% from this level. Special attention was given to establish a rugged assay that would be easily transferable between laboratories, and the recorded recoveries of 98.2–100.5% for both the formulated drug product and the drug substance during intermediate precision evaluation at different analysis situations indicated that this mission was accomplished. A multivariate assessment of intermediate precision data acquired using an experimental design scheme revealed that the assay was not adversely affected by any of the situation variables, including the use of different liquid chromatography instrument types, regardless of if they were constructed from inert materials or stainless steel that had been passivated, even though such problems have been reported in several previous methods for analysis of foscarnet.Ngoc Phuoc DinhAdel ShamshirGjani HulajTobias JonssonMDPI AGarticledesign of experimentsfoscarnetmethod developmentmonograph modernizationpharmaceutical quality controlsuppressed ion chromatographyPhysicsQC1-999ChemistryQD1-999ENSeparations, Vol 8, Iss 209, p 209 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	design of experiments foscarnet method development monograph modernization pharmaceutical quality control suppressed ion chromatography Physics QC1-999 Chemistry QD1-999
spellingShingle	design of experiments foscarnet method development monograph modernization pharmaceutical quality control suppressed ion chromatography Physics QC1-999 Chemistry QD1-999 Ngoc Phuoc Dinh Adel Shamshir Gjani Hulaj Tobias Jonsson Validated Modernized Assay for Foscarnet in Pharmaceutical Formulations Using Suppressed Ion Chromatography Developed through a Quality by Design Approach
description	Inspired by the United States Pharmacopoeia (USP) “monograph modernization” initiative, we developed and validated an assay for foscarnet sodium injection solution (“foscavir”), following quality by design (QbD) principles, incorporating design of experiments (DoE) and multivariate data analysis to establish the design space and robust setpoint of the method. The resulting analytical procedure was based on ion chromatography (IC) with suppressed conductivity detection, employing an isocratic carbonate–bicarbonate eluent system. The assay was successfully validated at the robust setpoint conditions, according to the guidelines established by the International Council for Harmonization (ICH). The linear range stretched at least from 5 to 100 mg/L with high repeatability (relative standard deviation, RSD ≤ 0.3%) both at the target concentration (60 mg/L) and at 50% and 150% from this level. Special attention was given to establish a rugged assay that would be easily transferable between laboratories, and the recorded recoveries of 98.2–100.5% for both the formulated drug product and the drug substance during intermediate precision evaluation at different analysis situations indicated that this mission was accomplished. A multivariate assessment of intermediate precision data acquired using an experimental design scheme revealed that the assay was not adversely affected by any of the situation variables, including the use of different liquid chromatography instrument types, regardless of if they were constructed from inert materials or stainless steel that had been passivated, even though such problems have been reported in several previous methods for analysis of foscarnet.
format	article
author	Ngoc Phuoc Dinh Adel Shamshir Gjani Hulaj Tobias Jonsson
author_facet	Ngoc Phuoc Dinh Adel Shamshir Gjani Hulaj Tobias Jonsson
author_sort	Ngoc Phuoc Dinh
title	Validated Modernized Assay for Foscarnet in Pharmaceutical Formulations Using Suppressed Ion Chromatography Developed through a Quality by Design Approach
title_short	Validated Modernized Assay for Foscarnet in Pharmaceutical Formulations Using Suppressed Ion Chromatography Developed through a Quality by Design Approach
title_full	Validated Modernized Assay for Foscarnet in Pharmaceutical Formulations Using Suppressed Ion Chromatography Developed through a Quality by Design Approach
title_fullStr	Validated Modernized Assay for Foscarnet in Pharmaceutical Formulations Using Suppressed Ion Chromatography Developed through a Quality by Design Approach
title_full_unstemmed	Validated Modernized Assay for Foscarnet in Pharmaceutical Formulations Using Suppressed Ion Chromatography Developed through a Quality by Design Approach
title_sort	validated modernized assay for foscarnet in pharmaceutical formulations using suppressed ion chromatography developed through a quality by design approach
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/0422a0794f784914bec856f13daacb59
work_keys_str_mv	AT ngocphuocdinh validatedmodernizedassayforfoscarnetinpharmaceuticalformulationsusingsuppressedionchromatographydevelopedthroughaqualitybydesignapproach AT adelshamshir validatedmodernizedassayforfoscarnetinpharmaceuticalformulationsusingsuppressedionchromatographydevelopedthroughaqualitybydesignapproach AT gjanihulaj validatedmodernizedassayforfoscarnetinpharmaceuticalformulationsusingsuppressedionchromatographydevelopedthroughaqualitybydesignapproach AT tobiasjonsson validatedmodernizedassayforfoscarnetinpharmaceuticalformulationsusingsuppressedionchromatographydevelopedthroughaqualitybydesignapproach
_version_	1718410443689558016

Validated Modernized Assay for Foscarnet in Pharmaceutical Formulations Using Suppressed Ion Chromatography Developed through a Quality by Design Approach

Ejemplares similares