Wakefield Chemistry Consulting LLC, Bel Air, Maryland 21015, United States.
J Med Chem. 2024 Oct 10;67(19):16991-16999. doi: 10.1021/acs.jmedchem.4c01694. Epub 2024 Oct 2.
A recent review identified the problem of lower isotopologues in deuterated active pharmaceutical ingredients (APIs) as a critical issue in this area of medicinal chemistry. In this Perspective, the relationship between overall enrichment and isotope distribution for deuterated APIs is discussed. Deuterated APIs are divided into single deuterium, methyl-d, and polydeuterated compounds. For the latter category, distribution calculations demonstrate that the parent deuterated API contains significant quantities of the lower isotopologues. As an alternative to the use of overall enrichment to describe these compounds, it is suggested that describing these compounds with a distribution profile should be preferred, giving an accurate and defensible description of the API. Using this approach, the lower isotopologues become an integral part of the API and not an impurity.
最近的一篇综述指出，氘代活性药物成分（APIs）中较低同位素丰度的问题是药物化学领域的一个关键问题。在本观点中，讨论了氘代 API 的整体丰度与同位素分布之间的关系。氘代 API 分为单氘代、甲基-d 和多氘代化合物。对于后一类，分布计算表明，母体氘代 API 中含有大量的低同位素丰度物质。作为使用整体丰度来描述这些化合物的替代方法，建议使用分布谱来描述这些化合物，从而对 API 进行准确且有说服力的描述。使用这种方法，较低同位素丰度物质成为 API 的一个组成部分，而不是杂质。
