Investigation of the Metabolic Biotransformation of CCK-4 in Liver Microsomes of Human, Monkey, Rat, and Mouse Using Ultra-Performance Liquid Chromatography-High-Resolution Mass Spectrometry
Abstract
The goal of this study was to establish cholecystokinin tetrapeptide (CCK-4) metabolic stability in liver microsomes from four species (human, monkey, rat, and mouse) and identify and characterize CCK-4 metabolites using liquid chromatography tandem mass spectrometry. Endogenous peptide metabolism is not well documented, and this is particularly true for neuropeptide CCK-4. In vitro, the metabolism of CCK-4 followed first-order kinetics, and the half-lives were 51.7, 36.7, 27.3, and 36.7 min for human (HLM), monkey (MyLM), rat (RLM), and mouse (MsLM) liver microsomes, respectively. The half-life of CCK-4 in HLMs was greater than that in MyLMs, RLMs, and MsLMs, which suggested that CCK-4 was metabolically more stable in HLMs. The degradation of CCK-4 was correlated with rapidly appearing metabolites in the incubation mixture, which suggested that the metabolites would be present in the systemic circulation. Six major metabolites were identified and quantified, and the measured metabolite concentrations indicated that significant differences in the CCK-4 metabolic profile exist between species.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2018
- Accession Number
- AD1056077
Entities
People
- Frederic Berg
- Li Kong
Organizations
- Edgewood Chemical Biological Center