Enantiomeric separation of verapamil and norverapamil using Chiral-AGP® as the stationary phase

Simultaneous quantification of the enantiomers of verapamil and its N-demethylated metabolite in human plasma using liquid chromatography–tandem mass spectrometry

“…In the previous work by Sandström et al [18], a mobile phase around pH 7 and acetonitrile as the organic modifier, were found to be optimal for the simultaneous chiral separation of verapamil and norverapamil using the Chiral-AGP ® column and UV detection. This optimised separation method could however not be directly transferred to electrospray mass spectrometry (ESI-MS), as the mobile phase contained the poorly volatile phosphate buffer.…”

“…Different types of chiral stationary phases (CSPs) have been used for this purpose. Both CSPs based on cellulose derivatives like Chiralpak AD ® [6,7] and Chiralcel OD ® [8,9], as well as protein-based ones like ␣ 1 -acid glycoprotein (Chiral-AGP ® ) [10][11][12][13][14][15] and ovomucoid [16][17][18] have in these studies demonstrated enantioselectivity towards verapamil. One obstacle, however, especially when using protein-based CSPs, has been the chromatographic interference with the metabolite norverapamil.…”

“…Separation systems based on liquid chromatography with UV or fluorescence detection, have earlier been developed in order to individually determine the enantiomers of verapamil in biological samples [6][7][8][9][10][11][12][13][14][15][16][17][18]. Different types of chiral stationary phases (CSPs) have been used for this purpose.…”

“…This problem has been solved by increasing the selectivity using a combination of achiral and chiral chromatography [6,10,11,[14][15][16][17] or by chemical derivatisation (acetylation) of norverapamil [12,13]. However, in one study, a chemometric approach has been used to optimise a chromatographic separation of both the enantiomers of verapamil and norverapamil using a single column system (Chiral-AGP ® ) without derivatisation [18]. The use of a mass spectrometer as the detector for the chiral LC system would facilitate the situation, as there would be no need for chromatographic separation between the main component and its metabolites as long as they differ in molecular mass.…”

Thin‐layer chromatography separation of enantiomers of verapamil using macrocyclic antibiotic as a chiral selector

“…resolution by HPLC without derivatization using a chiralcel OD-RH column (Ho et al, 2000), cellulose/amylose phase (Perrin et al, 2002), a chiral-AGP column (Sandstro et al, 1999), a chiral OD-R column (Asafu-Adjaye et al, 1998), 2,6-di-O-carboxylmethyl-β-cyclodextrin (Li et al, 1997), α 1 -acid glycoprotein (Rustichelli et al, 1997;Stagni et al, Silica gel G, with 13% calcium sulfate as binder, having chloride, iron and lead impurities up to 0.02% and showing pH 7.0 in a 10% aqueous suspension, was from E. Merck (Bombay, India). Other reagents and chemicals used were of analytical reagent grade and were obtained from SISCO Research Laboratory (Bombay, India), BDH (Central Drug House, New Delhi, India) and E. Merck (Bombay, India).…”