The impact of radiochemistry in drug projects: The use of C-14 label in the AZD8529, AZD7325, and AZD6280 projects.
Lee P KingstonChungang GuJian GuoSteve SwallowCharles S ElmorePublished in: Journal of labelled compounds & radiopharmaceuticals (2021)
Understanding the metabolic transformations of a potential drug molecule is important to understanding the safety profile of a drug candidate. Liquid chromatography-mass spectrometry is a standard method for detecting metabolites in the drug discovery stage, but this can lead to an incomplete understanding of the molecule's metabolism. In this manuscript, we highlight the role radiolabeling played in determining the metabolism and in quantifying the metabolites of AZD8529, AZD7325, and AZD6280. A quantitative whole-body autoradiography study can detect covalent adducts in vivo as was the case with AZD5248 in which the compound was bound to the aorta. Ultimately another compound free of aortic binding was developed, AZD7986.
Keyphrases
- mass spectrometry
- liquid chromatography
- drug discovery
- high resolution
- aortic valve
- ms ms
- quality improvement
- emergency department
- pulmonary artery
- heart failure
- tandem mass spectrometry
- high resolution mass spectrometry
- climate change
- transcription factor
- coronary artery
- gas chromatography
- aortic dissection
- dna binding