Simultaneous Determination of Escitalopram Impurities Including the R-Enantiomer on a Cellulose Tris(3,5-Dimethylphenylcarbamate)-Based Chiral Column in Reversed-Phase Mode

Szabó, Zoltán -. István and Bartalis-Fábián, Ágnes and Tóth, Gergő (2022) Simultaneous Determination of Escitalopram Impurities Including the R-Enantiomer on a Cellulose Tris(3,5-Dimethylphenylcarbamate)-Based Chiral Column in Reversed-Phase Mode. SSRN ELECTRONIC JOURNAL (SOCIAL SCIENCE RESEARCH NETWORK). ISSN 1556-5068 (Submitted)

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Abstract

A high-performance liquid chromatographic method was developed for the simultaneous determination of the related substances – three potential chemical impurities from escitalopram synthesis -, and the enantiomeric purity of escitalopram. The separation capacity of seven different polysaccharide-type chiral columns, including three amylose-based (Lux Amylose-1, Lux i-Amylose-1, Lux Amylose-2) and four cellulose-based (Lux Cellulose-1, Lux Cellulose-2, Lux Cellulose-3 and Lux Cellulose-4) were screened in polar organic, and reversed-phase mode. Lux Cellulose-1, based on cellulose tris(3,5-dimethylphenylcarbamate) as chiral selector with acetonitrile-water mixture containing 0.1% diethylamine was identified as the most promising system. Using “one factor at a time” optimization technique the effect of column temperature, flow rate and mobile phase constituents on separation performance was checked and the critical resolution values were determined. U-shaped retention pattern was obtained when plotting the retention factors of the citalopram enantiomers versus the water content of the binary mobile phases on Lux Cellulose-1 column. Thermodynamic analysis revealed an enthalpy-driven enantioseparation in polar organic and in reversed-phase mode as well. For further method optimizations a L9 orthogonal array table was employed. Using the optimized parameters (Lux Cellulose-1 column with 0.1% (v/v) diethylamine in water/acetonitrile 55/45 (v/v), 0.8 mL/min flow rate at 25 °C) baseline separation were achieved between all compounds. Our newly developed HPLC method was validated according to the ICH guidelines and its application was tested on a pharmaceutical formulation and proved to be suitable for routine quality control of related substances and the enantiomeric purity of escitalopram.

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