Economical and rapid enantioselective, diastereoselective and achiral separation of palonosetron hydrochloride and its impurities using supercritical fluid chromatography.

Autor: Qiu X; Institute of Medicinal Biotechnology, Peking Union Medical College & Chinese Academy of Medical Sciences, Tian Tan Xi Li No.2, Beijing 100050, PR China., Liu Y; Institute of Medicinal Biotechnology, Peking Union Medical College & Chinese Academy of Medical Sciences, Tian Tan Xi Li No.2, Beijing 100050, PR China., Zhao X; Institute of Medicinal Biotechnology, Peking Union Medical College & Chinese Academy of Medical Sciences, Tian Tan Xi Li No.2, Beijing 100050, PR China., Lian X; Institute of Medicinal Biotechnology, Peking Union Medical College & Chinese Academy of Medical Sciences, Tian Tan Xi Li No.2, Beijing 100050, PR China., Xing J; Xinjiang Key Laboratory of Uygur Medical Research, Xinjiang Institute of Materia Medica, Xinhua South Road No.140, Urumqi 830004, PR China., Zheng R; Xinjiang Key Laboratory of Uygur Medical Research, Xinjiang Institute of Materia Medica, Xinhua South Road No.140, Urumqi 830004, PR China., Yao J; China National Institutes for Food and Drug Control, Tian Tan Xi Li No.1, Beijing 100050, PR China. Electronic address: yaojh@nifdc.org.cn., Shan G; Institute of Medicinal Biotechnology, Peking Union Medical College & Chinese Academy of Medical Sciences, Tian Tan Xi Li No.2, Beijing 100050, PR China. Electronic address: shanguangzhi@imb.pumc.edu.cn.
Jazyk: angličtina
Zdroj: Journal of chromatography. A [J Chromatogr A] 2024 Nov 08; Vol. 1736, pp. 465342. Date of Electronic Publication: 2024 Sep 04.
DOI: 10.1016/j.chroma.2024.465342
Abstrakt: Simultaneous separation of compounds with multiple chiral centers and highly similar structures presents significant challenges. This study developed a novel supercritical fluid chromatography (SFC) method with reduced organic solvent consumption and robust separation capabilities to address these challenges. The method was applied to simultaneously achieve enantioselective, diastereoselective, and achiral separation of palonosetron hydrochloride and its six impurities. The effects of the polysaccharide-based chiral stationary phase (CSP), modifier, additive, and column temperature on retention and separation were comprehensively evaluated. It was found that a combination of a polysaccharide-based CSP and a single modifier or a mixture of protonic modifiers could not achieve complete separation due to high structural similarity. However, an ADH column and a ternary solvent mixture containing acetonitrile (methanol: acetonitrile: diethylamine, 60:40:0.2, v/v/v) provided satisfying separation, particularly for the enantiomer and diastereomers of palonosetron. Using the optimized method, the enantioselective, diastereoselective, and achiral separation of palonosetron hydrochloride and its six impurities can be accomplished in 18 min under gradient elution. Thermodynamic results indicated that the separation process was entropy driven. A molecular docking study revealed that the separation was mainly achieved through the differences in hydrogen bond and π - π interactions between the analytes and CSP. This study lays the foundation for SFC analysis of palonosetron hydrochloride and provides a reference for the simultaneous SFC separation of the enantiomers, diastereoisomers and structurally similar compounds.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: