Department of Chemistry, Biology and Biotechnology, University of Perugia, Via Elce di Sotto 8, 06123 Perugia, Italy.
Molecular Horizon SRL, Via Montelino 30, 06084 Bettona, Italy.
J Chem Inf Model. 2021 Jun 28;61(6):2706-2719. doi: 10.1021/acs.jcim.1c00226. Epub 2021 Jun 1.
Stress testing is one of the most important parts of the drug development process, helping to foresee stability problems and to identify degradation products. One of the processes involving stress testing is represented by forced degradation studies, which can predict the impact of certain conditions of pH, moisture, heat, or other negative effects due to transportation or packaging issues on drug potency and purity, ensuring patient safety. Regulatory agencies have been working on a standardization of laboratory procedures since the past two decades. One of the results of those years of intensive research is the International Conference on Harmonization (ICH) guidelines, which clearly define which forced degradation studies should be performed on new drugs, which become a routine work in pharmaceutical laboratories. Since used techniques based on high-performance liquid chromatography coupled with high-resolution mass spectrometry have been developed years ago and are now mastered by pharmaceutical scientists, automation of data analysis, and thus data processing, is becoming a hot topic nowadays. In this work, we present MassChemSite and WebChembase as a tandem to automatize the routine analysis studies without missing information quality, using as a case study the degradation of lansoprazole under acidic, oxidative, basic, and neutral stress conditions.
应力测试是药物开发过程中最重要的部分之一，有助于预测稳定性问题，并识别降解产物。涉及应力测试的过程之一是强制降解研究，它可以预测 pH 值、湿度、热等特定条件或由于运输或包装问题对药物效力和纯度的影响，从而确保患者的安全。监管机构在过去二十年一直在对实验室程序进行标准化。这些年深入研究的结果之一是国际协调会议（ICH）指南，该指南明确规定了应在新药上进行哪些强制降解研究，这些研究已成为制药实验室的常规工作。由于多年前已经开发出基于高效液相色谱与高分辨率质谱联用的现有技术，并且现在已被制药科学家掌握，因此数据分析的自动化，从而数据处理，已成为当今的热门话题。在这项工作中，我们提出了 MassChemSite 和 WebChembase 作为串联，以在不影响信息质量的情况下实现常规分析研究的自动化，以兰索拉唑在酸性、氧化、碱性和中性应激条件下的降解为例进行研究。
