Stereospecific Determination of Sertraline and its Impurities in Bulk Drug Using Cyclodextrins as a Chiral Selector

Author(s): Navjot Kaur Sandhu, Durga Das Angehore, Neeraj Upmanyu, Pawan K. Porwal*

Journal Name: Current Pharmaceutical Analysis

Volume 16 , Issue 7 , 2020

Become EABM
Become Reviewer

Graphical Abstract:


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.

Keywords: Sertraline, Cis and Trans isomers, -CD, HP -CD, HPLC, sertraline hydrochloride.

Jhonson, B.M.; Chang, P.T.L. Monograph of sertraline Hydrochloride in: analytical profile of drug substances and excipients; harry, g. brittain,, ed.; academic press,oval road, london, 1996, 24, pp. 443-486.
Nageswara Rao, R.; Nagaraju, V. An overview of the recent trends in development of HPLC methods for determination of impurities in drugs. J. Pharm. Biomed. Anal., 2003, 33(3), 335-377.
[] [PMID: 14550856]
monograph of sertraline. united state pharmacopeia-national formulary, united state pharmacopeial convention, 2017, 3-2,6146-49.,
monograph of sertraline. the british pharmacopoeia, medi-cines and healthcare products regulatory agency (mhra), 2017, 2,824-26..
monograph of sertraline.the indian pharmacopoeia, the indi-an pharmacopoeia commission,, (7th ed. ) 2014, 2, 824-826.
Ameyibor, E.; Stewart, J.T. Enantiomeric HPLC separation of selected chiral drugs using native and derivatized β-cyclodextrins as chiral mobile phase additives. J. Liq. Chromatogr. Relat. Technol., 2006, 20, 855-869.
Kafková, B.; Bosáková, Z.; Tesarová, E.; Coufal, P.; Messina, A.; Sinibaldi, M. Vancomycin as chiral selector for enantioselective separation of selected profen nonsteroidal anti-inflammatory drugs in capillary liquid chromatography. Chirality, 2006, 18(7), 531-538.
[] [PMID: 16634133]
Fujimura, K.; Suzuki, S.; Hayashi, K.; Masuda, S. Retention behavior and chiral recognition mechanism of several cyclodextrinbonded stationary phases for dansyl amino acids. Anal. Chem., 1990, 62, 2198-2205.
Snyder, L.R.; Krikland, J.J.; Glajch, J.H. Practical HPLC method development, 2nd ed; Wiley-Blackwell: New York, 1997.
Rao, R.N.; Talluri, M.V.N.K.; Maurya, P.K. Separation of stereoisomers of sertraline and its related enantiomeric impurities on a dimethylated β-cyclodextrin stationary phase by HPLC. J. Pharm. Biomed. Anal., 2009, 50(3), 281-286.
[] [PMID: 19502000]
Passos, J.J.; De Sousa, F.B.; Lula, I.S.; Barreto, E.A.; Lopes, J.F.; De Almeida, W.B.; Sinisterra, R.D. Multi-equilibrium system based on sertraline and β-cyclodextrin supramolecular complex in aqueous solution. Int. J. Pharm., 2011, 421(1), 24-33.
[] [PMID: 21963467]
Chen, D.; Jiang, S.; Chen, Y.; Hu, Y. HPLC determination of sertraline in bulk drug, tablets and capsules using hydroxypropyl-β-cyclodextrin as mobile phase additive. J. Pharm. Biomed. Anal., 2004, 34(1), 239-245.
[] [PMID: 14738940]
Lucangioli, S.E.; Hermida, L.G.; Tripodi, V.P.; Rodríguez, V.P.; López, E.E.; Rouge, P.D.; Carducci, C.N. Analysis of cis-trans isomers and enantiomers of sertraline by cyclodextrin-modified micellar electrokinetic chromatography. J. Chromatogr. A, 2000, 871(1-2), 207-215.
[] [PMID: 10735301]
Kano, K. Mechanisms for chiral recognition by Cyclodextrins. J. Phys. Org. Chem., 1997, 10, 286.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Published on: 17 August, 2020
Page: [823 - 830]
Pages: 8
DOI: 10.2174/1573412915666190312164301
Price: $65

Article Metrics

PDF: 23