HPLC-fluorescence detection for stability of harringtonine, and identification of degradation products by UPLC-Q-TOF-MS.

Autor: Gao J; School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China., Su X; School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China., Lei P; School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China., Liang J; School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China., Ren B; School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China., Zhang Y; School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China., Ma X; School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China., Zhang Y; School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China; Department of Medical Oncology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an Jiaotong University, Xi'an 710061, China., Ma W; School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: maweina2015@xjtu.edu.cn.
Jazyk: angličtina
Zdroj: Journal of pharmaceutical and biomedical analysis [J Pharm Biomed Anal] 2024 Mar 15; Vol. 240, pp. 115927. Date of Electronic Publication: 2023 Dec 19.
DOI: 10.1016/j.jpba.2023.115927
Abstrakt: Harringtonine (HT) is an anticancer alkaloid early extracted and isolated from cephalotaxus fortunei Hook. f., also has various pharmacological activities such as antiviral, antibacterial, antimalarial, anti-inflammatory, antioxidant, herbicidal and insecticidal. However, the factors affecting the stability of HT, the main degradation sites and mechanisms involved in its disposal process in vivo have not yet been elucidated. This study utilized HPLC-fluorescence detection method to establish a simple quantitative detection method for HT with good accuracy, precision, and high sensitivity. Temperature and pH were the main factors affecting the stability of HT, which underwent significant degradation in high temperature and alkaline environments because of the occurrence of hydrolysis reactions. In isolated biological homogenates of SD rats, except gastrointestinal tract, HT was degraded in other sites, especially respiratory, mainly in airway and lungs, and systemic metabolism, mainly in livers, spleens, and kidneys. Through UPLC-Q-TOF-MS, three forced degradation products were identified as 4'-demethyl HT, cephalotaxine, and dehydrated HT, respectively. However, the degradation product in isolated biological homogenates of SD rats was only 4'-demethyl HT due to the relatively mild environment. Our findings contributed to a necessary study basis for HT in terms of structural optimization, dosage form selection, storage and transportation.
Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests..
(Copyright © 2023 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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