<p></p><p>A new,
cost-effective and fast chromatographic method using sulfated β-cyclodextrin
(SβCD) as a chiral mobile phase additive (CMPA) was developed and validated for
the enantiomeric separation of milnacipran. Milnacipran is an anti-depressant
drug. Levo-milnacipran is the active enantiomer with less adverse effects than
dextro-milnacipran. Hence, it is imperative to separate the enantiomers of
milnacipran. Various parameters affecting enantiomeric resolution, for
instance, the effect of type and concentration of cyclodextrins, the effect of
pH of the mobile phase, effect of type and concentration of the organic solvent
in the mobile phase and effect of type of achiral column, were investigated. We
demonstrated successful resolution of enantiomers of milnacipran on
reverse-phase HPLC with Kinetex C8 column (150x4.6mm, 5µ), using a mobile phase
consisting of 18:82 v/v acetonitrile: 10mM sodium dihydrogen orthophosphate
dihydrate buffer pH 3.0 (adjusted with orthophosphoric acid) containing 10mM
SβCD with a flow rate 1.0 ml/minute. The column temperature was ambient and UV
detection was carried out at 227 nm with an injection volume of 20µl. This
method for enantiomeric separation of milnacipran was validated in accordance
with ICH guidelines and successfully applied to the marketed formulation of
Levomilnacipran. Furthermore, molecular docking was used to identify the chiral
recognition mechanism. The results of molecular docking corroborated with our
experimental findings.</p><br><p></p>
HR-DOSY and sulfoxide enantiomeric discrimination by cyclodextrin
