Graduate School of Pharmacy, Gujarat Technological University, Gandhinagar, Gujarat, India.
School of Applied Sciences and Technology, Gujarat Technological University, Ahmedabad, Gujarat, India.
Rapid Commun Mass Spectrom. 2024 Oct 15;38(19):e9884. doi: 10.1002/rcm.9884.
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.
亚硝胺类化合物是潜在的致癌物质，引起了监管机构的高度关注，特别是在药物中存在的亚硝胺类化合物。雷尼替丁中发现了不可接受水平的 N-亚硝基二乙胺（NDMA），导致了广泛的召回，这促使人们对替代药物如尼扎替丁产生了兴趣，尼扎替丁与雷尼替丁具有相似的药理学分类，用于治疗各种胃肠道疾病。尽管关于尼扎替丁中 NDMA 水平的报告较少，但它与雷尼替丁的结构相似，都具有叔胺，这突出了形成 NDMA 的潜力。为了解决与亚硝胺检测相关的分析挑战，本研究专注于开发和验证一种超高效液相色谱三重四极杆质谱（UHPLC-MS/MS）方法，用于定量测定尼扎替丁原料药和片剂制剂中的 NDMA。方法验证符合国际协调会议的建议，NDMA 的线性范围为 0.25-100ng/mL，表现出极好的线性（回归系数>0.999）和高效回收率，范围为 95.98%-109.57%。该方法具有很高的灵敏度，检测限和定量限分别为 0.25 和 0.5ng/mL。所开发的 UHPLC-MS/MS 方法为监测澳大利亚可用的尼扎替丁制剂中的 NDMA 水平提供了一种简单、精确、准确和选择性的方法，具有增强的灵敏度和特异性，定量限在 ppb 和亚 ppb 范围内。
