Abstract：
For the approval of a drug, the stability data must be submitted to regulatory authorities. Such analyses are often time-consuming and cost-intensive. Forced degradation studies are mainly carried out under harsh conditions in the dissolved state, often leading to extraneous degradation profiles for a solid drug. Oxidative mechanochemical degradation offers the possibility of generating realistic degradation profiles. In this study, a sustainable mechanochemical procedure is presented for the degradation of five active pharmaceutical ingredients (APIs) from the sartan family: losartan potassium, irbesartan, valsartan, olmesartan medoxomil, and telmisartan. High-resolution mass spectrometry enabled the detection of impurities already present in untreated APIs and allowed the elucidation of degradation products. Significant degradation profiles could already be obtained after 15-60 min of ball milling time. Many of the identified degradation products are described in the literature and pharmacopoeias, emphasizing the significance of our results and the applicability of this approach to predict degradation profiles for drugs in the solid state.
摘要：
为了批准一种药物，稳定性数据必须提交给监管机构。这种分析通常是耗时且成本密集的。强制降解研究主要在溶解状态的苛刻条件下进行，通常导致固体药物的外来降解。氧化机械化学降解提供了产生现实降解曲线的可能性。在这项研究中,提出了一种可持续的机械化学程序，用于降解来自沙坦家族的五种活性药物成分（API）：氯沙坦钾，厄贝沙坦,缬沙坦,奥美沙坦酯,还有替米沙坦.高分辨率质谱能够检测未经处理的API中已经存在的杂质，并能够阐明降解产物。在球磨时间15-60分钟后，已经可以获得明显的降解曲线。许多鉴定的降解产物在文献和药典中有描述，强调我们的结果的重要性和该方法预测药物在固态降解曲线的适用性。
