Deuterated active pharmaceutical ingredients: A science-based proposal for synthesis, analysis, and control. Part 1: Framing the problem
Deuterated active pharmaceutical ingredients: A science-based proposal for synthesis, analysis, and control. Part 1: Framing the problem
复制标题
DOI：
10.1002/jlcr.3743
复制
发表时间：
2019-09-01
影响因子：
1.8
通讯作者：
Wang, Peng
中科院分区：
文献类型：
--
作者：
Czeskis, Boris;Elmore, Charles S.;Wang, Peng
国际药物开发创新与质量联盟（IQ）最近成立了一个工作组，专注于制定处理氘化活性药物成分的指南。在某些情况下，活性药物成分（API）的氘化可以通过利用初级动力学同位素效应来延缓和/或改变API的代谢。几种氘化原料药已经进入临床，其中一种最近获得批准。在大多数情况下，合成100%同位素纯的化合物是非常困难的，几乎不可能。这就提出了综合的、分析的和监管的问题，需要对综合方法、分析方法和规范进行基于科学的评估和建议。一个由同位素化学、过程化学、分析化学、药物代谢和药代动力学等领域的科学家组成的跨职能团队在IQ的主持下召开了会议，以确定和解决这些问题。本文努力构建化学，制造和控制挑战。
The International Consortium for Innovation & Quality (IQ) in Pharmaceutical Development recently established a working group focused on the development of a guidance to address Deuterated Active Pharmaceutical Ingredients. Deuteration of an Active Pharmaceutical Ingredient (API) in some cases can retard and/or alter API metabolism by exploiting the primary kinetic isotope effect. Several deuterated APIs have entered into the clinic, and one has recently been approved. In most cases, it is very difficult to nearly impossible to synthesize a 100% isotopically pure compound. This raises synthetic, analytical, and regulatory questions that warrant a science-based assessment and recommendations for synthetic methods, analytical methods, and specifications. A cross functional team of scientists with expertise in isotope chemistry, process chemistry, analytical chemistry, and drug metabolism and pharmacokinetics have been meeting under the auspices of IQ to define and address these questions. This paper strives to frame chemistry, manufacturing, and controls challenges.