Influence of the inorganic counterion on the chiral micellar electrokinetic separation of basic drugs using the surfactant N-dodecoxycarbonylvaline.

The chiral surfactant N-dodecoxycarbonylvaline (DDCV) has previously been used with a sodium counterion in micellar electrokinetic chromatography (MEKC) separations of beta-blockers (pindolol, atenolol, metoprolol, acebutolol, alprenolol, oxprenolol and propranolol), beta-agonists (N-methylpseudoephedrine, pseudoephedrine, ephedrine and norephedrine) and phenolic amino alcohols (norphenylephrine, synephrine, octopamine and salbutamol) in this laboratory. In the present study, we investigated the effects of three monovalent counterions--Li+, Na+ and K+--on the peak shape, efficiency, selectivity and retention of these 15 chiral pharmaceutical compounds with DDCV micelles. A much better (more symmetrical) peak shape was observed when Li+ was employed, due to a better if still imperfect match of analyte and counterion mobilities; average asymmetry factors in LiDDCV, NaDDCV, and KDDCV buffers were 1.9, 3.7, and 4.2, respectively. An increase in efficiency of 50-100% for hydrophobic solutes and over 100% for many hydrophilic solutes was also observed in LiDDCV compared to NaDDCV and KDDCV, probably due to enhanced mass transfer. The influence of an organic modifier (acetonitrile) in the separation buffer was also studied for the LiDDCV, NaDDCV and KDDCV systems. Although a concentration of either 0 or 5% acetonitrile resulted in the best enantiomeric resolution for most analytes, the most hydrophobic solutes (alprenolol and propranolol) required the addition of 20-25% ACN. Due to differences in the conductance of Li+, Na+ and K+, the advantage of using Li+ as the counterion for anionic DDCV micelles (better peak shape, higher efficiency and resolution, with shorter analysis times), although apparent for comparisons at a given applied voltage, is more significant when considered in the more appropriate context of equivalent Joule heating.