The purpose of this study was to elucidate the effect of high-temperature storage on the stability of ranitidine, specifically with respect to the potential formation of N-nitrosodimethylamine (NDMA), which is classified as a probable human carcinogen. Commercially available ranitidine reagent powders and formulations were stored under various conditions, and subjected to LC-MS/MS analysis. When ranitidine tablets from two different brands (designated as tablet A and tablet B) were stored under accelerated condition (40 °C with 75% relative humidity), following the drug stability guidelines issued by the International Conference on Harmonisation (ICH-Q1A), for up to 8 weeks, the amount of NDMA in them substantially increased from 0.19 to 116 ppm and from 2.89 to 18 ppm, respectively. The formation of NDMA that exceeded the acceptable daily intake limit (0.32 ppm) at the temperature used under accelerated storage conditions clearly highlights the risk of NDMA formation in ranitidine formulations when extrapolated to storage under ambient conditions. A forced-degradation study under the stress condition (60 °C for 1 week) strongly suggested that environmental factors such as moisture and oxygen are involved in the formation of NDMA in ranitidine formulations. Storage of ranitidine tablets and reagent powders at the high temperatures also increased the amount of nitrite, which is considered one of the factors influencing NDMA formation. These data indicate the necessity of controlling/monitoring stability-related factors, in addition to controlling impurities during the manufacturing process, in order to mitigate nitrosamine-related health risks of certain pharmaceuticals.

这项研究的目的是阐明高温储存对雷尼替丁稳定性的影响，特别是在氮的潜在形成方面-亚硝基二甲胺（NDMA），被归类为可能的人类致癌物。将可商购的雷尼替丁试剂粉末和制剂在各种条件下保存，并进行LC-MS / MS分析。当按照国际协调会议（ICH-Q1A）发布的药物稳定性指南，将两种不同品牌的雷尼替丁片剂（分别称为片剂A和片剂B）在加速条件（40°C，相对湿度为75％）下存储时，在长达8周的时间里，其中的NDMA量分别从0.19分别增加到116 ppm和从2.89增加到18 ppm。超过可接受的每日摄入量限制（0。在加速储存条件下使用的温度（32 ppm）明显突出了雷尼替丁制剂在环境条件下储存时形成NDMA的风险。在压力条件下（60°C，持续1周）进行的强制降解研究强烈表明，雷尼替丁制剂中NDMA的形成涉及水分和氧气等环境因素。雷尼替丁片和试剂粉在高温下的存储也增加了亚硝酸盐的含量，这被认为是影响NDMA形成的因素之一。这些数据表明，除了在制造过程中控制杂质外，还需要控制/监测与稳定性有关的因素，以减轻某些药物与亚硝胺有关的健康风险。