Shivani Tanwar

Direct TLC resolution of atenolol and propranolol into their enantiomers using three different chiral selectors as impregnating reagents.

Direct resolution of racemic atenolol and propranolol into their enantiomers was achieved by normal phase TLC on silica gel plates impregnated with optically pure L-tartaric acid, (R)-mandelic acid and (-)-erythromycin as chiral selectors. Different solvent systems were worked out to resolve the enantiomers. Spots were detected using iodine vapour. The TLC method was validated for linearity, limit of detection and limit of quantification. The influence of pH, temperature and concentration of chiral selector was studied.

Different approaches of impregnation for resolution of enantiomers of atenolol, propranolol and salbutamol using Cu(II)-L-amino acid complexes for ligand exchange on commercial thin layer chromatographic plates.

Atenolol and propranolol (the beta-blocking agents) and salbutamol (broncho- and vasodilator) were resolved into their enantiomers by adopting different modes of loading/impregnating the Cu(II) complexes of L-proline (L-Pro), L-phenylalanine (L-Phe), L-histidine (L-His), N,N-dimethyl-L-phenylalanine (N,N-Me(2)-L-Phe), and L-tryptophan (L-Trp) on commercial precoated normal phase plates. The three different approaches were (A) using the Cu(II)-L-amino acid complex as chiral mobile phase additive, (B) ascending development of plain commercial plates in the solutions of Cu complex, and (C) using a solution of Cu(II) acetate as mobile phase additive for the commercial TLC plates impregnated with ascending development of plates in the solutions of amino acid. Spots were located using iodine vapour. The results obtained for the three methods have been compared for their efficiency and the issue of involvement of the Cu(II) cation for the best performance of the three methods has been discussed with respect to the same mobile phase. The detection limit is 0.18 microg for each enantiomer.

Synthesis of succinimidyl-(S)-naproxen ester and its application for indirect enantioresolution of penicillamine by reversed-phase high-performance liquid chromatography

Synthesis of N-succinimidyl-(S)-2-(6-methoxynaphth-2-yl) propionate was carried out by the reaction of (S)-naproxen with N-hydroxysuccinimide in the presence of dicyclohexyl carbodiimide. It was characterized and was used as a chiral derivatizing reagent, under mild conditions, to form diastereomers of dl-penicillamine which were resolved by reversed-phase high-performance liquid chromatography using triethyl ammonium phosphate buffer (pH 4.0, 5mM)-acetonitrile (linear gradient (30min) of acetonitrile from 30 to 70%). Excellent separation was achieved with gradient mobile phase. The detection limit was at pmol level.

Reversed‐phase high‐performance liquid chromatographic enantioresolution of six β‐blockers using dinitrophenyl‐l‐Pro‐N‐hydroxysuccinimide ester, N‐succinimidyl‐(S)‐2‐(6‐methoxynaphth‐2‐yl) propionate and twelve variants of Sanger's reagent as chiral derivatizing reagents

Twelve chiral derivatizing reagents (CDRs) were synthesized by substituting one of the fluorine atoms in 1,5-difluoro-2,4-dinitrobenzene (DFDNB) with three optically pure amines [(R)-(-)-1-cyclohexylethylamine, (+)-dehydroabietylamine and (S)-(-)-alpha,4-dimethylbenzylamine], six amino acid amides [L-Ala-NH(2), L-Phe-NH(2), L-Val-NH(2), L-Leu-NH(2), L-Met-NH(2) and D-Phg-NH(2)] and three amino acids [L-Ala, L-Val and L-Leu]. In addition, dinitrophenyl-L-Pro-N-hydroxysuccinimide ester and N-succinimidyl-(S)-2-(6-methoxynaphth-2-yl) propionate were also synthesized and used as CDR. Keeping in view the presence of an amino group, diastereomers of six beta-blockers (atenolol, propranolol, bisoprolol, metoprolol, salbutamol, and carvedilol) were synthesized by reaction with these 14 CDRs. The diastereomers were separated by RP-HPLC. The method was validated for linearity, accuracy, limit of detection and limit of quantification.

Synthesis of dinitrophenyl-L-Pro-N-hydroxysuccinimide ester and four new variants of Sanger's reagent having chiral amines and their application for enantioresolution of mexiletine using reversed-phase high-performance liquid chromatography

Four chiral derivatizing reagents (CDRs) having enantiomerically pure amines and two CDRs namely, [N-succinimidyl-(S)-2-(6-methoxynaphth-2-yl)propionate], and [dinitrophenyl-L-Pro-N-hydroxysuccinimide ester, DNP-L-Pro-SU] were synthesized and were used to prepare diastereomers of (R,S)-mexiletine (MEX); these were separated by reversed-phase high-performance liquid chromatography (RP-HPLC). The method was validated for linearity, accuracy, limit of detection (LOD) and limit of quantification (LOQ).

Reversed-phase liquid chromatographic determination of enantiomers of atenolol in rat plasma using derivatization with Marfey's reagent

An HPLC method was established for enantioseparation of (R,S)-atenolol (ATE) and determination of enantiomers in rat plasma. Marfeys reagent (1-fluoro-2,4-dinitrophenyl-5-L-alanine amide, FDNP-L-Ala-NH(2), MR) was used as chiral derivatizing reagent with detection of diastereomers at 340 nm. It was shown that the R-isomer eluted before the S-isomer. The method was validated for linearity, repeatability, limits of detection and limit of quantification (LOQ). Recovery of ATE at LOQ was 92.8% for (R)-ATE and 92.6% for (S)-ATE.