High‐performance liquid chromatographic enantioseparation of (R,S)‐fluoxetine using Marfey's reagent and (S)‐N‐(4‐nitrophenoxycarbonyl) phenylalanine methoxyethyl ester as chiral derivatizing reagents along with direct thin‐layer chromatographic resolution and isolation of enantiomers using l‐tartaric acid as mobile phase additive

Abstract

Chiral assay of enantiomers of fluoxetine was achieved in pharmaceutical formulations using direct and indirect methods. L-tartaric acid was used as a mobile phase additive in thin-layer chromatography; the enantiomers were separated and isolated and were used to determine the elution order in HPLC. (R,S)-flouxetine was derivatized with (S)-N-(4-nitrophenoxycarbonyl)phenylalanine methoxyethyl ester [(S)-NIFE], Marfey's reagent and 1-fluoro-2,4-dinitrophenyl-L-methionine amide (FDNP-L-Met-NH₂. The diastereomers were separated using RP-HPLC. The effect of flow rate and TFA concentration on resolution was studied. The diastereomers obtained by derivatization with FDNP-L-Met-NH₂ were also separated by RP-TLC.

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

“…The present method has advantages over earlier reports as the derivatization takes only a few seconds in comparison with other conventional techniques (mentioned above); for example, the synthesis of the diastereomers of ( RS )‐Flx using Marfey's reagent required 1 h stirring of the reaction mixture (Bhushan and Agarwal, ). The H‐Phth group, in CDR3 (Nap‐Phth), underwent nucleophilic substitution by Flx via its amino group.…”

“…CSP columns are expensive, however, and may often not be sufficiently stable. Liquid chromatographic enantioseparation of ( RS )‐Flx by an indirect approach has been reported using ( R )‐1‐(1‐naphthyl)‐ethyl isocyanate (Unceta et al ., ; Potts and Parli, ), Marfey's reagent and ( S )‐ N ‐(4‐nitrophenoxycarbonyl) phenylalaninemethoxyethyl ester (Bhushan and Agarwal, ) as CDRs.…”

Analytical methodologies for the stereoselective determination of fluoxetine: An overview

“…In another report, Bhushan and Agarwal () published the chiral derivatization of racemic FLX with ( S )‐NIFE, Marfey's reagent and FDNP‐ l ‐Met‐NH 2 . The diastereomers were separated using RP‐HPLC.…”

EnantioselectiveLCanalysis and determination of selective serotonin reuptake inhibitors

“…Direct TLC enantiomeric separation of ( RS )‐Flx (along with isolation of native enantiomers) was achieved (Bhushan & Agarwal, ) using homemade TLC plates (10 × 5 cm × 0.5 mm) prepared by spreading the slurry of silica‐gel G with an applicator on glass plates which were activated overnight at 60 ± 2°C before use. Solutions of racemic Flx (5 × 10 −2 m in methanol) were applied (2 μL, 25 nmol) to the plates.…”