Deuterated active pharmaceutical ingredients: A science-based proposal for synthesis, analysis, and control. Part 1: Framing the problem.
International Consortium for Innovation & Quality
active pharmaceutical ingredient
deuterium
drug substance
isotopologue
isotopomer
kinetic isotope effect
stable-isotope
Journal
Journal of labelled compounds & radiopharmaceuticals
ISSN: 1099-1344
Titre abrégé: J Labelled Comp Radiopharm
Pays: England
ID NLM: 7610510
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
04
03
2019
revised:
12
04
2019
accepted:
23
04
2019
pubmed:
30
4
2019
medline:
21
5
2020
entrez:
30
4
2019
Statut:
ppublish
Résumé
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.
Substances chimiques
Pharmaceutical Preparations
0
Deuterium
AR09D82C7G
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
690-694Informations de copyright
© 2019 John Wiley & Sons, Ltd.
Références
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IUPAC Compendium of Chemical Terminology Gold Book Version 2.3.3 24 Feb 2014. Pure and Appl. Chem. 1979;51:353-380. Note that this team is focused only on isotopomers and isotopologues of starting materials, intermediates, and active pharmaceutical ingredients; isotopomers and isotopologues of impurities are out of scope (considered to be impurities of impurities).