Enantioseparation of (RS)-etodolac was achieved by an indirect approach. Extraction of the drug (RS)-etodolac (Etd) was done from commercially available tablets, as its racemic mixture; it was purified, characterized, and was used for enantioseparation studies. Diastereomeric amides of (RS)-Etd were synthesized using a commercial sample of enantiomerically pure (R)-(−)-1-cyclohexylethylamine. Derivatization reactions were carried out under conditions of stirring at room temperature (30°C for 2 h) for (RS)-Etd and under microwave irradiation (MWI). The derivatives (as diastereomeric amides) were separated by thin-layer chromatography (TLC). The successful solvent system for separating the diastereomeric amides of (RS)-Etd was acetonitrile—methanol—dichloromethane—water (6:1:1:0.5, v/v). Spots were located by use of iodine vapor. The diastereomeric amides were recovered by preparative method; these were purified and characterized by recording their m.p., λmax (ultraviolet [UV]), infrared (IR) spectra, specific rotation, and proton nuclear magnetic resonance (1H-NMR) spectra for the verification of the synthesis and for the separation of diastereomeric amides.
Authors:Hariom Nagar, Jürgen Martens, and Ravi Bhushan
Enantioresolution of three active pharmaceutical ingredients (APIs), namely, atenolol, betaxolol, and orciprenaline, marketed as racemic mixture, has been achieved in a direct mode using (S)-glutamic acid as chiral additive in thin-layer chromatography. Two different approaches were adopted: (1) (S)-glutamic acid was mixed in the silica gel slurry for making thin-layer plates, or (2) it was added in the mobile phase and plain plates without any chiral additive were used. Both (1) and (2) were capable of separating enantiomers of all the three racemates, but different combinations and proportions of solvents were found successful in the two cases. Good resolution was achieved in both cases, and the results are compared for these two sets of studies among themselves and with other literature reports. Iodine was used to locate the spots of the corresponding enantiomers. The detection limits for each enantiomer were found in the range of 1.4–1.9 μg (per spot).
Authors:Ravi Bhushan, Hans Brückner, Virender Kumar, and Deepak Gupta
A simple and rapid method has been established for indirect separation of the optical isomers of seventeen DL
amino acids by reversed-phase and normal-phase TLC. Amino acids derivatized with 1-fluoro-2,4-dinitrophenyl-5-L
), or 1-fluoro-2,4-dinitrophenyl-5-L
) were spotted on precoated plates. Diastereomers of all the DL
amino acids were separated most effectively by normal-phase TLC with phenol-water, 3:1 (
), as mobile phase. In reversed-phase TLC the diastereomers were separated most effectively by use of mobile phases containing acetonitrile and triethylamine-phosphate buffer (50 mM, pH 5.5). The results obtained by use of the classical
) were compared with those obtained by use of FDNP-L
. The effects of buffer concentration, pH, and concentration of organic modifier were studied. This indirect method enabled resolution of DL
amino acids at nanomolar concentrations.
Direct resolution of enantiomers of (RS)-ketorolac was achieved by thin-layer chromatography on silica gel plates using enantiomerically pure L-tryptophan, L-valine, L-methionine, and L-histidine as chiral additive in the stationary phase. The solvent system (acetonitrile, methanol water, and chloroform) with different ratios was successful in resolving the enantiomers. Spots were detected by use of iodine vapor. The detection limit was 0.4 µg mL−1 for each enantiomer of (RS)-ketorolac. The native enantiomers were isolated and characterized.