In Situ Derivatization of (RS)-Mexiletine and Enantioseparation Using Micellar Liquid Chromatography: A Green Approach

Developing surfactant-based aqueous solvents as alternatives to organic solvents for chromatographic enantioseparation is highly desired. Surfactants are inexpensive, nontoxic, environmental friendly, and increase the solubility of organic compounds in aqueous solutions. In this work, the impact of surfactant-based aqueous solvents on RP-HPLC enantioseparation of (RS)-mexiletine is studied. The in situ derivatization of (RS)-mexiletine with chirally pure moieties [(S)-levofloxacin, (S)-ketoprofen, (S)-ibuprofen)] was carried out/performed to reduce consumption of organic solvents and side wastes, and to maintain a green approach. We report the impact of increasing concentration of surfactants on separation of diastereomeric derivatives of (RS)-mexiletine on a C-18 column of HPLC. Surfactant in water increased the solubility of a diastereomeric derivative, provided the lowest elution time (t(R) between 2.152 and 10.87 min), and minimized the consumption of solvent. The use of surfactant-containing aqueous mobile phases in chromatographic separations is a good alternative for replacement of organic solvents. The hydrolysis of the synthesized diastereomeric derivatives was carried out, and native enantiomers of mexiletine were isolated and characterized. In addition, the lowest-energy optimized structures were developed using the Gaussian 09 Rev. A.02 program for determination of elution order, and the method was validated for linearity, accuracy, limit of detection (LOD), and limit of quantitation (LOQ).