Background: Sertraline Hydrochloride, an oral anti-depressant, has two chiral centers and its
cis enantiomers and trans diasteromers are defined as related substances by United State Pharmacopoeia
and British Pharmacopoeia.
Introduction: A selective, stereospecific and economical high performance liquid chromatographic
(HPLC) method was developed for the determination of sertraline enantiomeric forms. The HPLC-UV
method was developed and optimized in the terms of system suitability parameters.
Methods: The elution was made using a mixture of -cyclodextrin (-CD) and hydroxypropyl -
cyclodextrin (HP -CD). Analysis was performed on a Zorbax SB C-18 column (250 x 4.6mm), 5μ with
the mobile phase consisting of 170mM KH2PO4 containing -CD and HP -CD (pH: 3.0 with dil. H3PO4)
and acetonitrile (75:25, v/v). Flow rate was kept at 1.0mL/min and the detection was carried out by UV
at 220nm. Enantio-separation for sertraline was carried out using two different CDs (β-CD and HP β-
CD) at different concentrations in the mobile phase.
Results: Complete resolution of all the four isomers was achieved using 9mM β-CD and 15mM HP β-
CD in the mobile phase. The development was optimized using central composite quadric model, where
concentration of -CD and HP -CD were varied and resolution between trans diastereomeric impurities
was calculated as a response.
Conclusion: Resolution between any pair of isomers was found to be more than 2. Method development
and optimization leading to the best resolution between the isomers of sertraline is described in detail.