Abstract

Characterization of Drug Metabolites and Degradation Products using LC-ESI-MS/MS

R Srinivas, Chief Scientist & HOD, Indian Institute of Chemical Technology

Over the years, stress studies of drugs have been recognized as an essential part of the drug development process. These studies are used to investigate the intrinsic stability of the drugs and provide the foundation for the development of a selective stability indicating assay method (SIAM). Stress testing is also useful for the formulation and packaging development, shelf-life determination and designing of manufacturing processes. As per regulatory guideline stress degradation studies and structural characterization should be carried out to establish degradation pathways of the drug, which is essential from both quality and safety point of view. Drug metabolism and pharmacokinetic (DMPK) study is another important aspect of early drug discovery process to optimize new chemical entities. These metabolism studies involve metabolic stability, cytochrome P450 (CYP) induction or inhibition and metabolite identi?cation. Metabolite identification is the most important part of drug metabolism. Identification of reactive metabolites is essential to avoid the toxicity and helps to modify the structure. Liquid chromatography electrospray ionization tandem mass spectrometry (LC-MS/MS, MSn) combined with H/D exchange experiments is the most popular analytical technique for identification and structural characterization drug degradation products and metabolites. This lecture will focus on some of our recent studies at IICT on stress studies and in vivo metabolic investigation of drug molecules which have been carried out using liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS).