Rendering A Chiral Screening Step In Supercritical Fluid Chromatography Mass-Spectrometry Compatible.

Nowadays, sensitive chiral methods are required for the determination of chiral impurities and for assays in biological samples. Supercritical fluid chromatography (SFC), one of the main techniques to separate chiral molecules, can be coupled to MS to provide such sensitive methods. Moreover, chiral separation strategies are very useful to reduce the development time and cost of such methods. This study investi- gates the transfer of an existing non-MS compatible screening step (as part of a separation strategy) into an MS-compatible one. The initial step had a cumulative success rate of 100 % for 57 tested compounds using methanol or 2-propanol as mobile phase modifier on one of four chiral stationary phases. The ad- ditives applied in the original mobile phases, i.e. isopropylamine and trifluoroacetic acid, negatively affect the ionization in SFC-MS and thus need to be replaced. Formic acid, acetic acid, water, ammonia, ammo- nium acetate and ammonium formate were investigated as MS-compatible additives in different combi- nations and concentrations. Only methanol-based mobile phases were considered in this study because high system pressures were obtained with isopropanol. The other experimental parameters remained the same as in the initial screening step. The effects of the alternative additives on the obtained resolutions as well as on the global success rate were investigated. The best alternative MS-compatible mobile phase contained 0.5 % CH 3 COOH and 40 mM NH 3 as additives. This mobile phase provided the highest num- ber of separations and rather high resolutions. An MS-compatible screening step was defined with this alternative mobile phase. Compared to the original additives, a similar success rate was obtained.

Publication year:2020

Keywords:Chiral separations; Supercritical fluid chromatography; Transfer; Additive screening; MS-compatible chiral screening step

CSS-citation score:1

Accessibility:Open