Chromatographic Separation of Verapamil Racemate Using a Varicol Continuous Multicolumn Process

Abstract

-Verapamil is a chiral drug that is marketed in its racemic form, but because of the pharmacological effects due to molecule's chirality, one of the enantiomers is more potent, and the other exhibits different activities of therapeutic interest. The preparative separation of the verapamil enantiomers was performed using a continuous Varicol unit operated on a scale of 1 g/day. Amylose tris(3,5-dimethylphenylcarbamate) functioned as the stationary phase, and n-hexane/isopropanol/ethanol mixtures were used as the mobile phase. Diethylamine was used as the additive. The enantiomeric purities were 93.0% for S-(-)-verapamil and 92.0% for R-(+)-verapamil in the raffinate and extract streams, respectively. The unit provided productivities of 0.18 kg of raffinate per day per kg of adsorbent and 0.20 kg of extract per day per kg of adsorbent when using a feed concentration of 12.5 g L -1 .

Chiral Separations in Preparative Scale: A Medicinal Chemistry Point of View

“…LC has a key role for medicinal chemists, being a crucial tool for the preparative enantioseparation in all stages of drug discovery and development [27,38] (Figure 1). Diverse technological options can be applied for the separation of enantiomers in a preparative scale, including classical batch column chromatography [39,40], recycling loop chromatography [41,42], VARICOL (multicolumn continuous chromatography, an improved version of SMB) technology [43,44], among others. LC has benefited from enormous development for the last four decades, generating vast technical experience and amount of scientific data reported in literature.…”