Modern Developments In Isotopic Labelling

By Dr. Sean L. Kitson, Investigator, Prof. Tom Moody Head of Biocatalysis,  Dr. William Watters, Isotope Chemistry Manager at Almac

The success of a drug candidate to reach the market requires a rigorous investigation into its toxicological profile. Therefore, ADME (Absorption, Distribution, Metabolism and Excretion) studies must be executed at an early stage in the clinical development of the investigational drug. The data obtained from these metabolism studies will enable a decision on whether to proceed to more advanced costly clinical trials. In order to carry out a metabolism study it is necessary to incorporate specific isotopic label(s) into the investigational drug.

This approach can use both stable and radioactive isotopes. However, radioisotopes are more utilised since the detection of radioactivity is easier and more sensitive. In ADME studies the excretory products (e.g. blood and urine) are collected and analysed by several techniques to identify in vivo metabolites.

To take account of these factors a stable labelled version of the drug is required to complement the radiolabelled version. Carbon-13 labelled drug versions are preferred as there is always the possibility that hydrogen exchange with deuterium can occur with its surroundings.