Novel method for monitoring of carcinogenic impurity of N-nitrosamine in nizatidine pharmaceutical products using ultra high-pressure liquid chromatography triple quadrupole mass spectrometry.

Autor: Dhorajiya S; Graduate School of Pharmacy, Gujarat Technological University, Gandhinagar, Gujarat, India., Goswami J; Graduate School of Pharmacy, Gujarat Technological University, Gandhinagar, Gujarat, India., Dudhatra B; School of Applied Sciences and Technology, Gujarat Technological University, Ahmedabad, Gujarat, India., Thummar K; Graduate School of Pharmacy, Gujarat Technological University, Gandhinagar, Gujarat, India.
Jazyk: angličtina
Zdroj: Rapid communications in mass spectrometry : RCM [Rapid Commun Mass Spectrom] 2024 Oct 15; Vol. 38 (19), pp. e9884.
DOI: 10.1002/rcm.9884
Abstrakt: Nitrosamine compounds pose a significant concern as potential carcinogens, prompting heightened scrutiny from regulatory bodies, particularly regarding their presence in pharmaceuticals. The detection of unacceptable levels of N-nitrosodiethylamine (NDMA) in ranitidine has led to widespread recalls, driving interest in alternative medications such as nizatidine, which shares a similar pharmacological class and is used to treat various gastrointestinal conditions. Despite fewer reports on NDMA levels in nizatidine, its structural similarity to ranitidine, characterized by a tertiary amine, underscores the potential for NDMA formation. Addressing the analytical challenges associated with nitrosamine detection, this study focuses on developing and validating an ultra-high pressure liquid chromatography triple quadrupole mass spectrometry (UHPLC-MS/MS) method for quantifying NDMA in both nizatidine active pharmaceutical ingredients and tablet formulations. Method validation adheres to International Council for Harmonisation recommendations, with a demonstrated linear range of 0.25-100 ng/mL for NDMA, exhibiting excellent linearity (regression coefficient >0.999) and efficient recovery rates ranging from 95.98% to 109.57%. The method shows high sensitivity, with limits of detection and quantification of 0.25 and 0.5 ng/mL, respectively. The developed UHPLC-MS/MS method offers a simple, precise, accurate, and selective approach for monitoring NDMA levels in nizatidine formulations available in Australia, promising enhanced sensitivity and specificity with limits of quantification in the ppb and sub-ppb ranges.
(© 2024 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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