Forced degradation of five drug substances for meRgeION validation

Drug substance is subjected to acid hydrolysis and oxidative stress against a baseline condition. The goal here is to profile and identify various degradation products of five APIs by setting stress conditions more severe than recommended storage, in order to further understand the underlying chemical mechanisms Non-targeted profiling in DDA mode was conducted for samples at Day 0 (1 sample) and Day 7 (3 samples for 3 conditions) on Orbitrap Fusion Lumos. Converted data files were submitted to MZMine for feature detection. Folder change of each feature under different conditions was calculated in excel. We then built a LC-MS/MS data processing pipeline in meRgeION that enables degradation product annotation by searching the spectral database Drug+ (lib_drug_plus_matrix.RData) and mechanism understanding through FBMN.

药物活性成分在基线条件下承受酸性水解和氧化应激。本研究的目的是通过设置比推荐储存条件更为严苛的应力条件，以表征和识别五种活性药物成分（API）的多种降解产物，进而深入理解其背后的化学机制。在非靶向分析模式下，对第0天（1个样本）和第7天（3种条件下的3个样本）的样品在Orbitrap Fusion Lumos上进行DDA（深度发展分析）模式下的非靶向分析。转换后的数据文件被提交至MZMine进行特征检测。在Excel中计算了不同条件下每个特征文件夹的变化。随后，我们在meRgeION中构建了一个液相色谱-质谱-质谱（LC-MS/MS）数据处理流程，该流程通过搜索光谱数据库Drug+（lib_drug_plus_matrix.RData）实现降解产物的注释，并通过FBMN（故障树模型网络）进行机制理解。