SFC-MS; Vitamin D3; Oily drug products; Impurities; Quality control; Validation
Abstract :
[en] Vitamin D3, an essential micronutrient, often requires supplementation via medicines or food supplements, which necessitate quality control (QC). This study presents the development of a method for detecting and quantifying seven impurities of vitamin D3 in oily drug products using supercritical fluid chromatography–mass spectrometry (SFC-MS). Targeted impurities include two esters of vitamin D3 and five non-esters including four that are isobaric to vitamin D3. Firstly, a screening study highlighted the Torus 1-AA column and acetonitrile modifier as adequate for the separation, followed by optimization of the SFC conditions. Secondly, make-up solvent composition and MS settings were optimized to reach high sensitivity. For both the separation and MS response, the screening design of experiments proved useful. Lastly, a fast saponification and liquid–liquid extraction method was developed, enabling efficient sample cleanup and impurities recovery from the complex oily matrix. The SFC-MS method suitability was assessed in two validation studies. The first study employed the ICH Q2 guideline for impurity limit test to demonstrate method specificity and establish a limit of detection (LOD) and a limit of quantification (LOQ) at 0.2% and 0.5%, respectively, for ester impurities. The second study conducted a comprehensive quantitative assessment for three non-ester impurities using a total error approach, determining method validity through accuracy profiles. The validated method exhibited reliable performance across impurity concentrations from 0.1% to 2.0%, with estimated LODs ranging from 2 to 7 ng/mL. This study further promotes SFC-MS as a valuable, versatile, and green tool for routine pharmaceutical QC.
Research Center/Unit :
CIRM - Centre Interdisciplinaire de Recherche sur le Médicament - ULiège
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Jambo, Hugues ; Université de Liège - ULiège > Département de pharmacie > Chimie analytique
Dispas, Amandine ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM) ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments ; Université de Liège - ULiège > Département de pharmacie > Chimie analytique
Pérez-Mayán, Leticia; Universidade de Santiago de Compostela, 15782-Santiago de Compostela, Spain > Department of Analytical Chemistry > Nutrition and Food Sciences. Research Institute on Chemical and Biological Analysis (IAQBUS)
Rodríguez, Isaac; Universidade de Santiago de Compostela, 15782-Santiago de Compostela, Spain > Department of Analytical Chemistry > Nutrition and Food Sciences. Research Institute on Chemical and Biological Analysis (IAQBUS)
Ziemons, Eric ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM) ; Université de Liège - ULiège > Département de pharmacie > Chimie analytique verte pharmaceutique ; Université de Liège - ULiège > Département de pharmacie > Chimie analytique
Hubert, Philippe ; Université de Liège - ULiège > Département de pharmacie > Chimie analytique ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Language :
English
Title :
Comprehensive analysis of vitamin D3 impurities in oily drug products using supercritical fluid chromatography–mass spectrometry
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