Identification and characterization of process related impurities in chloroquine and hydroxychloroquine by LC/IT/MS, LC/TOF/MS and NMR

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• 作者：Vaijanath G. Dongre ; Pradeep D. Ghugare ; Pravin Karmuse ; Dharmendra Singh ; Atul Jadhav ; Ashok Kumar
• 关键词：Chloroquine ; Hydroxychloroquine ; Impurities ; Identification ; Characterization
• 刊名：Journal of Pharmaceutical and Biomedical Analysis
• 出版年：2009
• 出版时间：1 May 2009
• 年：2009
• 卷：49
• 期：4
• 页码：873-879
• 全文大小：675 K

文摘

The focus of this study is identification and characterization of major unknown impurities in chloroquine (CQ) and hydroxychloroquine (HCQ) bulk drug samples using liquid chromatography/ion trap mass spectrometry (LC/IT/MS) and liquid chromatography/time of flight mass spectrometry (LC/TOF/MS). The newly developed LC/MS method was employed for the analysis of both the drugs. The analysis revealed the presence of two impurities in each of the drugs. The impurities are designated as CQ-I, CQ-II (for chloroquine); HCQ-I and HCQ-II (for hydroxychloroquine). Three of the impurities, CQ-II, HCQ-I and HCQ-II were unknown have not been reported previously. Accurate masses of the impurities were determined by using Q-TOF mass spectrometer and fragmentation behavior was studied by an ion trap mass spectrometer. Based on the spectrometric data and synthetic specifics the structures of CQ-II, HCQ-I and HCQ-II were proposed as 1,4 pentanediamine, N⁴(7-chloro-4-quinolinyl), N⁴-chloromethyl, N⁴-ethylamine; 2-(4-(7-chloroquinolin-4-ylamino) pentylamino) ethanol and [[4-[(7-chloro-4-quinolyl) amino] N-pentyl] N-chloromethyl-N-ethylamino] ethanol respectively. The impurities were isolated by semi-preparative HPLC and structures were confirmed by NMR spectroscopy. The formation and through characterization of known CQ-I impurity is also discussed.