Recent advances in analytical techniques for deuterium isotopic purity of deuterated drugs

Deuterated drugs have been new strategies in drug design and development for advantages in improving pharmacokinetic properties, reducing toxic metabolites, and stabilizing chiral structures over their non-deuterated counterparts. Deuterium isotopic impurities, including isotopologues and isotopomers, are inevitably generated even with state-of-the-art deuteration techniques, which significantly affect the safety and potency of drugs through deuterium kinetic isotope effects. Therefore, deuterium isotopic purity is the most characteristic critical quality attribute of deuterated drugs compared to other drugs. However, it is challenging to separate isotopic mixtures with routine analytical methods, and regulatory agencies have not proposed guidelines for deuterated drugs in terms of analytical techniques and quality control, which presents great analytical challenges for the development of deuterated drugs. This paper reviews the analytical techniques for deuterium isotopic purity of deuterated drugs and discusses the features and scopes of different methods. It aims to provide references for the development and relevant study of deuterated drugs.