Simultaneous Determination of Escitalopram Impurities including the <i>R</i>-enantiomer on a Cellulose tris(3,5-Dimethylphenylcarbamate)-Based Chiral Column in Reversed-Phase Mode
A high-performance liquid chromatographic method was developed for the simultaneous determination of the related substances—three potential synthesis-related chemical impurities and the distomer—of escitalopram. The separation capacity of seven different polysaccharide-type chiral columns, including...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/24/9022 |
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| author | Zoltán-István Szabó Ágnes Bartalis-Fábián Gergő Tóth |
| author_facet | Zoltán-István Szabó Ágnes Bartalis-Fábián Gergő Tóth |
| author_sort | Zoltán-István Szabó |
| collection | DOAJ |
| description | A high-performance liquid chromatographic method was developed for the simultaneous determination of the related substances—three potential synthesis-related chemical impurities and the distomer—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 columns (Lux Cellulose-1, Lux Cellulose-2, Lux Cellulose-3, and Lux Cellulose-4) were screened in the polar organic and reversed-phase modes. Lux Cellulose-1, based on cellulose tris(3,5-dimethylphenylcarbamate) as the chiral selector with an acetonitrile-water mixture containing 0.1% diethylamine was identified as the most promising separation system. Using the “one factor at a time” optimization approach, the effect of column temperature, flow rate, and mobile phase constituents on separation performance was evaluated, and the critical resolution values were determined. A 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 the Lux Cellulose-1 column. A thermodynamic analysis revealed enthalpy-driven enantioseparation in both the polar organic and reversed-phase modes. For further method optimizations, an L9 orthogonal array table was employed. Using the optimized parameters (Lux Cellulose-1 column with 0.1% (<i>v</i>/<i>v</i>) diethylamine in water/acetonitrile 55/45 (<i>v</i>/<i>v</i>); 0.8 mL/min flow rate at 25 °C), baseline separations were achieved between all compounds. Our newly developed HPLC method was validated according to the ICH guidelines and its application was tested with a commercially available pharmaceutical formulation. The method proved to be suitable for routine quality control of related substances and the enantiomeric purity of escitalopram. |
| first_indexed | 2024-03-09T16:02:49Z |
| format | Article |
| id | doaj.art-fb5a8e0a72d74d4b99478a8c4200b35a |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T16:02:49Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-fb5a8e0a72d74d4b99478a8c4200b35a2023-11-24T17:01:31ZengMDPI AGMolecules1420-30492022-12-012724902210.3390/molecules27249022Simultaneous Determination of Escitalopram Impurities including the <i>R</i>-enantiomer on a Cellulose tris(3,5-Dimethylphenylcarbamate)-Based Chiral Column in Reversed-Phase ModeZoltán-István Szabó0Ágnes Bartalis-Fábián1Gergő Tóth2Department of Pharmaceutical Industry and Management, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Gh. Marinescu 38, 540139 Targu Mures, RomaniaDepartment of Pharmaceutical Industry and Management, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Gh. Marinescu 38, 540139 Targu Mures, RomaniaDepartment of Pharmaceutical Chemistry, Semmelweis University, H-1085 Budapest, HungaryA high-performance liquid chromatographic method was developed for the simultaneous determination of the related substances—three potential synthesis-related chemical impurities and the distomer—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 columns (Lux Cellulose-1, Lux Cellulose-2, Lux Cellulose-3, and Lux Cellulose-4) were screened in the polar organic and reversed-phase modes. Lux Cellulose-1, based on cellulose tris(3,5-dimethylphenylcarbamate) as the chiral selector with an acetonitrile-water mixture containing 0.1% diethylamine was identified as the most promising separation system. Using the “one factor at a time” optimization approach, the effect of column temperature, flow rate, and mobile phase constituents on separation performance was evaluated, and the critical resolution values were determined. A 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 the Lux Cellulose-1 column. A thermodynamic analysis revealed enthalpy-driven enantioseparation in both the polar organic and reversed-phase modes. For further method optimizations, an L9 orthogonal array table was employed. Using the optimized parameters (Lux Cellulose-1 column with 0.1% (<i>v</i>/<i>v</i>) diethylamine in water/acetonitrile 55/45 (<i>v</i>/<i>v</i>); 0.8 mL/min flow rate at 25 °C), baseline separations were achieved between all compounds. Our newly developed HPLC method was validated according to the ICH guidelines and its application was tested with a commercially available pharmaceutical formulation. The method proved to be suitable for routine quality control of related substances and the enantiomeric purity of escitalopram.https://www.mdpi.com/1420-3049/27/24/9022citalopramLux Cellulose-1reversed-phase enantioseparationchemoselectivitychiral separation |
| spellingShingle | Zoltán-István Szabó Ágnes Bartalis-Fábián Gergő Tóth Simultaneous Determination of Escitalopram Impurities including the <i>R</i>-enantiomer on a Cellulose tris(3,5-Dimethylphenylcarbamate)-Based Chiral Column in Reversed-Phase Mode Molecules citalopram Lux Cellulose-1 reversed-phase enantioseparation chemoselectivity chiral separation |
| title | Simultaneous Determination of Escitalopram Impurities including the <i>R</i>-enantiomer on a Cellulose tris(3,5-Dimethylphenylcarbamate)-Based Chiral Column in Reversed-Phase Mode |
| title_full | Simultaneous Determination of Escitalopram Impurities including the <i>R</i>-enantiomer on a Cellulose tris(3,5-Dimethylphenylcarbamate)-Based Chiral Column in Reversed-Phase Mode |
| title_fullStr | Simultaneous Determination of Escitalopram Impurities including the <i>R</i>-enantiomer on a Cellulose tris(3,5-Dimethylphenylcarbamate)-Based Chiral Column in Reversed-Phase Mode |
| title_full_unstemmed | Simultaneous Determination of Escitalopram Impurities including the <i>R</i>-enantiomer on a Cellulose tris(3,5-Dimethylphenylcarbamate)-Based Chiral Column in Reversed-Phase Mode |
| title_short | Simultaneous Determination of Escitalopram Impurities including the <i>R</i>-enantiomer on a Cellulose tris(3,5-Dimethylphenylcarbamate)-Based Chiral Column in Reversed-Phase Mode |
| title_sort | simultaneous determination of escitalopram impurities including the i r i enantiomer on a cellulose tris 3 5 dimethylphenylcarbamate based chiral column in reversed phase mode |
| topic | citalopram Lux Cellulose-1 reversed-phase enantioseparation chemoselectivity chiral separation |
| url | https://www.mdpi.com/1420-3049/27/24/9022 |
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