Simultaneous HPLC Analysis of S- And R-Verapamil and Metabolites, S- And R-Norverapamil in Human Plasma

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

“…However, at 60 pg/sample (140 fmol/sample or 120 pg/ml plasma), both the accuracy and precision were acceptable for both enantiomers. This means that the method described in this paper was more sensitive than the earlier published ones using chiral LC with fluorescence detection for the determination of the enantiomers of verapamil (earlier published LOQ: 2 ng/ml [11], 2.5 ng/ml [6], 3 ng/ml [13], 10 ng/ml [9], 20 ng/ml [12], 25 ng/ml [10]) and/or norverapamil (earlier published LOQ: 2 ng/ml [13], 5 ng/ml [6], 10 ng/ml [9], 30 ng/ml [10], 50 ng/ml [12]) in human plasma. In a previous chiral LC-off line GC-MS study, the LOQ for the enantiomers of verapamil was 0.25 ng/ml [28].…”

“…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.…”

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).…”

Application of restricted access material (RAM) with precolumn-switching and matrix solid-phase dispersion (MSPD) to the study of the metabolism and pharmacokinetics of Verapamil

“…In the majority of the existing publications describing methods for the determination of Verapamil and its main metabolites in biological samples, high-performance liquid chromatography [5,6,7] and HPLC-MS [8,9,10] were used. For the analysis of low levels of metabolites and the parent compound in biological samples, sample preparation, such as extraction, preconcentration and clean-up steps, are often required to improve sensitivity and selectivity.…”