Abstract：
Peroxide-mediated oxidation of drug molecules is a known challenge faced throughout the pharmaceutical development pathway-from early-stage stability studies to manufacturing processes. During the initial development stage, the major source of peroxide is the formulation excipients, whether they are pre-loaded or generated in situ due to slow degradation, and in the late phase, peroxides can be introduced during sanitization processes or generated via cavitation. In essence, a control strategy for peroxide mitigation often becomes a critical quality attribute for successful drug development. To this end, quantitation of peroxide is essential to monitor the peroxide level to ensure product quality and proposed shelf-life. However, methods for reliable and robust quantitation to detect trace levels of peroxide in a complex drug product matrix become increasingly challenging. This article discusses three high-throughput assays based on absorbance, fluorescence and chemiluminescence measurements to detect peroxide at a low level and compares the methods through validation studies in water. Selected methods have also been tested to understand the forced degradation of model peptide drug products with spiked hydrogen peroxide. Peptide degradation profiles and residual peroxide levels are presented to provide an understanding of the suitability of the quantitation methods and their performance.
摘要：
过氧化物介导的药物分子氧化是整个药物开发途径面临的已知挑战-从早期稳定性研究到制造过程。在最初的发展阶段，过氧化物的主要来源是配方赋形剂，无论它们是预加载的还是由于缓慢的降解而在原位产生的，在后期阶段，过氧化物可以在消毒过程中引入或通过空化产生。实质上,减轻过氧化物的控制策略通常成为成功药物开发的关键质量属性。为此,定量的过氧化物是必不可少的监测过氧化物水平，以确保产品质量和建议的保质期。然而,可靠和稳健的定量方法来检测复杂药物产品基质中的痕量水平的过氧化物变得越来越具有挑战性。本文讨论了三种基于吸光度的高通量测定，荧光和化学发光测量以检测低水平的过氧化物，并通过水中的验证研究比较这些方法。还测试了选定的方法，以了解掺入过氧化氢的模型肽药物产品的强制降解。提出了肽降解曲线和残余过氧化物水平，以了解定量方法的适用性及其性能。
