Study on N-nitrosamine impurities in dipine drugs
WU Zhong-li
ZHENG Guo-gang
JIA Fei
LI Chen
ZHOU Jian
YU Cheng-xiong
GAO Ying
WANG Bo
LOU Jin-fang
Abstract：Objective:To research on active pharmaceutical ingredient(API)based NDSRI of dipine drugs.Methods:Using 14 dipine drugs as raw materials,the experiments were conducted to verify whether the corresponding API NDSRI could be generated through two different nitrosation reactions.Liquid chromatography-mass spectrometry(LC-MS)was used to monitor the impurities.Results:The reaction results indicate that no NDSRI were formed in all of the nitrosation reactions of 14 dipine drugs.Almost all of the dipine drugs did not undergo degradation under the conditions of method 1.Most of dipine drugs were oxidized to produce aromatization impurities under the conditions of method 2,some individual varieties,such as azelnidipine,barnidipine,nicardipine and cilnidipine,have undergone varying degrees of degradation,and the structures of these degraded impurities were ultimately determined to be non NDSRI through separation and structural confirmation.Conclusion:The 14 APIs of dipine drugs studied in this article did not produce NDSRI impurities in a nitrosation environment.Some varieties underwent nitrosation to produce non NDSRI after degradation.Therefore,it is also necessary to pay attention to the study of non NDSRI.
Keywords：dipines drugnitrosation reactionN-nitrosamines impuritiesaromatization impuritydegradation
Publication Date：2025-03-14
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：12( 541-552 )