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Deuterated active pharmaceutical ingredients: A science‐based proposal for synthesis, analysis, and control. Part 1: Framing the problem
Author(s) -
Czeskis Boris,
Elmore Charles S.,
Haight Anthony,
Hesk David,
Maxwell Brad D.,
Miller Scott A.,
Raglione Thomas,
Schildknegt Klaas,
Traverse John F.,
Wang Peng
Publication year - 2019
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3743
Subject(s) - chemistry , active ingredient , framing (construction) , combinatorial chemistry , pharmacology , medicine , engineering , structural engineering
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.