Above 50% of pharmaceuticals in use are chiral and nearly 70% are ionizable weak bases. Liophilic ions are currently used in reversed phase chiral liquid chromatography to improve separation of stereoisomers of basic analytes. In this study, we investigate the effect of concentration and type of liophilic ion mobile phase additives on chiral separation of basic stereoisomers (atenolol and fluoxetine) on a Chirobiotic V column in polar ionic mode . The stereoisomers were successfully resolved using 20 mM ammonium salt in methanol with pH adjusted using 0.005% formic acid. Resolution of the stereoisomers of atenolol and fluoxetine ranged from 1.09 to 2.23 and 0.80 to 1.81, respectively. The four ammonium salts decreased retention of the analytes according to the Hofmeister series as follows; Cl- > NO3- > HCOO- >CH3COO- with retention factor ranging from 0.11 to 2.07, respectively. We investigated the effect of amount of liophilic salt on enantioresolution, enantioselectivity and retention factor by decreasing their concentration in the mobile phase from 20 mM to 4 mM. The retention factor decreased with increasing concentration of the ammonium salts in the mobile phase. Using van't Hoff plots (ln k against 1/T), we determined the standard changes in enthalpy (?H�) and entropy (?S�) and they ranged from -4.99 to -0.63 kJ/mol and -11.82 to 9.47 J/mol, respectively. The van't Hoff plots showed that the chiral recognition mechanism in the presence of inorganic salts is enthalpy driven. These results suggest these liophilic ions influenced retention and separation through dynamic ion exchange with the basic analytes. Enantioseparation of atenolol and fluoxetine was improved by adding liophilic ions in PIM on a Chirobiotic V column.

Assessing the influence of liophilic ions in enantioseparation of basic pharmaceuticals by polar ionic mode liquid chromatography

248th National Meeting (2014)

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