Is supercritical fluid chromatography hyphenated to massspectrometry suitable for the quality control of vitamin D3 oilyformulations?

peer reviewedNowadays, many efforts are devoted to improve analytical methods regarding efficiency, analysis timeand greenness. In this context, Supercritical Fluid Chromatography (SFC) is often regarded as a goodalternative over Normal Phase Liquid Chromatography (NPLC). Indeed, modern SFC separations arefast, efficient with suitable quantitative performances. Moreover, the hyphenation of SFC to mass spec-trometry (MS) provides additional gains in specificity and sensitivity. The present work aims at thedetermination of vitamin D3 by SFC-MS for routine Quality Control (QC) of medicines specifically. Basedon the chromatographic parameters previously defined in SFC-UV by Design of Experiments (DoE) andDesign Space methodology, the method was adapted to work under isopycnic conditions ensuring a base-line separation of the compounds. Afterwards, the response provided by the MS detector was optimizedby means of DoE methodology associated to desirability functions. Using these optimal MS parameters,quantitative performances of the SFC-MS method were challenged by means of total error approachmethod validation. The resulting accuracy profile demonstrated the full validity of the SFC-MS method. It was indeed possible to meet the specification established by the European Medicines Agency (EMA) (i.e. 95.0 − 105.0% of the API content) for a dosing range corresponding to at least 70.0-130.0% of theAPI content. These results highlight the possibility to use SFC-MS for the QC of medicine and obviouslysupport the switch to greener analytical methods.First International In-SCrit n°121786