CHIRAL SEPARATION OF CITALOPRAM BY REVERSED PHASE HPLC USING SULFATED BETA CYCLODEXTRIN AS CHIRAL MOBILE PHASE ADDITIVE
Keywords:
Enantiomeric resolution, Citalopram enantiomers, Citalopram enantiomeric purity, Chiral additiveAbstract
Objective: To develop a simple and cost effective chiral HPLC method for the separation of citalopram (CIT) enantiomers using chiral mobile phase additives (CMPAs).
Methods: Sulfated beta cyclodextrin (S-β-CD) was synthesized in our laboratory and was evaluated as a CMPA. The parameters affecting the resolution were optimized. CIT enantiomers were resolved on an achiral Kromasil C8 column (150 mm × 4.6 mm, 5 µm) using methanol and 20 mM KH2PO4 (pH 3) containing 12 mM S-β-CD (35:65) as the mobile phase with a flow rate of 1 ml/min at 240 nm. Chiral resolution capacity of synthesized S-β-CD was compared to the marketed product. The method using synthesized S-β-CD as CMPA was validated and applied for the quantitative determination of CIT enantiomers in bulk drug and tablet formulation.
Results: Synthesized S-β-CD gave a better resolution than the marketed form. This method was validated as per ICH guidelines and was found to comply with the standard norms. A good linearity was observed in the concentration range of 1-30 µg/ml with R2= 0.9993 for both enantiomers. The limit of detection and limit of quantification was 0.0272 and 0.0824 μg/ml for the R-enantiomer and 0.0303 and 0.0920 μg/ml for the S-enantiomer respectively.
Conclusion: A rapid and cost effective RP-HPLC method was developed and validated as per ICH guidelines to separate the CIT enantiomers. The method could be successfully applied for the quantitative determination of CIT enantiomers in bulk drug samples and pharmaceutical formulations.
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