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• Use of SFC in routine analysis for the QC of medicines and food supplements. • "Dilute-and-shoot" approach as preparation technique for complex samples in SFC. • Matrix effect was monitored and compared between different types of oily matrices. • Implementation of a control strategy based on a three-level SST. • Differences in manufacturing and QC suggested between medicines and food supplements. Vitamin D 3 is a key micronutrient whose intakes are inadequate for most populations worldwide. Supplementation with medicines or food supplements is commonly prescribed to correct this imbalance and the quality of these products must be ensured. In this context, a generic methodology for the assay of vitamin D 3 in oily formulations is proposed using supercritical fluid chromatography coupled to mass spectrometry (SFC-MS). It is in line with green analytical chemistry principles and combines the use of i) a fast and robust analytical method (4.0 min analysis time) ii) an easy sample preparation compatible with high throughput analysis ("dilute-and-shoot" approach) and iii) a relevant control strategy. Seventeen products from multiple manufacturers and encompassing a large content range were evaluated in this study. They were classified in four groups to streamline their processing considering the use of a matrix-matched calibration procedure. Matrix effect was thoroughly studied and was found to be low (99–106%), stable intra/inter-series and comparable between the different groups and types of matrices. The implemented control strategy was based on a three-level system suitability tests (SST). Level 1 SST: resolution of the critical pair that was above 1.5 for all analysis series. Level 2 SST: evaluation of the adequacy of the calibration for a QC sample in terms of recovery that was between 97% and 104% with a variability between 1% and 2%. Level 3 SST: method trueness that was between 95% and 102%. Sample analysis highlighted differences in types of products and dosage forms. This is the first study to propose a complete strategy for the quality control of vitamin D 3 oily formulations and should prove useful in QC laboratories. [ABSTRACT FROM AUTHOR]

Abstract: This paper focuses on implementing a design space approach and on the critical process parameters (CPPs) to consider when applying the Quality by Design (QbD) concepts outlined in ICH Q8(R2), Q9 and Q10 to analytical method development and optimization for three chiral compounds developed as modulators of small conductance calcium-activated potassium (SK) channels. In this sense, an HPLC method using a polysaccharide-based stationary phase containing a cellulose tris (4-chloro-3-methylphenylcarbamate) chiral selector in polar organic solvent chromatography mode was considered. The effects of trifluoroacetic acid (TFA) and n-hexane concentration in an acetonitrile (MeCN) mobile phase were investigated under a wide range of column temperatures. Good correlations were found between the observed data obtained after using a central composite design and the expected chromatographic behaviours predicted by applying the design of experiments-design space (DoE-DS) methodology. The critical quality attribute represented here by the separation criterion (S crit) allowed assessing the quality of the enantioseparation. Baseline separation for the compounds of interest in an analysis time of less than 20min was possible due to the original and powerful tools applied which facilitated an enhanced method comprehension. Finally, the advantage of the DoE-DS approach resides in granting the possibility to concurrently assess robustness and identify the optimal conditions which are compound dependent. [Copyright &y& Elsevier]