Liquid chromatographic enantioseparation of (RS)‐mexiletine and (RS)‐fluoxetine using chiral derivatizing reagents synthesized with (S)‐naproxen moiety

Abstract

Enantiomeric separation of racemic mexiletine and fluoxetine was achieved using three chiral derivatizing reagents (CDRs) based on (S)-naproxen. Diastereomers were synthesized by reaction of mexiletine or fluoxetine with the CDRs and were separated on a C18 column under reversed-phase conditions using a binary mixture of acetonitrile and triethylammonium phosphate/water, with UV detection at 230 and 226 nm. The results obtained for enantioseparation of the two drugs using the three CDRs were compiled and compared. The conditions for derivatization and chromatographic separation were optimized. The method was validated for linearity, repeatability, limit of detection and limit of quantification.

(RS)‐Propranolol: enantioseparation by HPLC using newly synthesized (S)‐levofloxacin‐based reagent, absolute configuration of diastereomers and recovery of native enantiomers by detagging

“…The separation factors (α, 1.23-1.61) for the diastereomers prepared with the newly synthesized CDRs were found to be better than the diastereomers prepared with CDRs based on (S)-naproxen (Batra and Bhushan, 2014;Bhushan and Nagar, 2014b), and CDRs having L-amino acids as chiral auxiliary in cyanuric chloride (Bhushan and Dixit, 2012), DFDNB (Bhushan and Tanwar, 2009; N-Benzotriazolyl-(S)-9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-3,7- Bhushan and Nagar, 2014a) and isothiocyanate (Kleidernigg et al, 1996;Péter and Fülöp, 2002). The newly synthesized CDRs were found to provide better Rs (2.91-4.71) in comparison with the resolution reported in the literature (Bhushan and Tanwar, 2009;Bhushan and Dixit, 2012;Péter and Fülöp, 2002;Péter et al, 2001;Kleidernigg et al,1996;Büschges et al, 1996); for example, Rs was 2.34 and 3.23 using (R)-MBIC and (S)-NEIC as CDRs, respectively (Bhushan and Dubey, 2011).…”

RP‐HPLC enantioseparation of β‐adrenolytics using micellar mobile phase without organic solvents

“…In addition, CDRs based on ( S )‐(−)‐Lfx, reported herein, were found to be more stable (>6 months at 2–5°C) as compared to CDRs based on DFDNB (Bhushan & Nagar, ; Bhushan & Tanwar, ) and isothiocyanate (Kleidernigg, Posch, & Lindner, ; Péter & Fülöp, ; Péter, Gyéresi, & Fülöp, ). In comparison to literature reports, the method was successful in providing very low LOD and LOQ values, better resolution (Batra & Bhushan, ; Bhushan & Dixit, ; Bhushan & Dubey, ; Bhushan & Tanwar, ; Büschges, Linde, Mutschler, & Spahn‐Langguth, ; Kleidernigg et al, ; Péter & Fülöp, ; Péter et al, ). Low retention times obtained in these studies resulted into lesser consumption of the mobile phase as well.…”

“…Low retention times obtained in these studies resulted into lesser consumption of the mobile phase as well. The separation factors (α) for the diastereomeric derivatives prepared with the CDR1 and CDR2 were found to be better than those for the diastereomeric derivatives prepared with CDRs based on ( S )‐naproxen (Batra & Bhushan, ; Bhushan & Nagar, ), and CDRs having l ‐amino acids as chiral auxiliary in cyanuric chloride (Bhushan & Dixit, ), DFDNB (Bhushan & Nagar, ; Bhushan & Tanwar, ) and isothiocyanate (Kleidernigg et al, ; Péter & Fülöp, ).…”

Analytical methodologies for the stereoselective determination of fluoxetine: An overview

“…Batra and Bhushan () proposed the enantioseparation of mexiletine and FLX using three chiral derivatizing agents based on the anti‐inflammatory drug S ‐naproxen. Diastereomers were prepared and separated on a C 18 column under RP‐LC using a binary mixture of acetonitrile and triethylammonium phosphate–water, with UV detection.…”