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Abstract

AN OVERVIEW OF GLUCURONIDATION IN DRUG METABOLIC REACTIONS AND ITS METABOLITES IDENTIFICATION BY CHROMATOGRAPHIC METHODS

Laximan Velip, Srikanth P., Sitesh Sah, Shraddha Jain, Surya Narayana P., Rajeshwari Rathod*

ABSTRACT

Metabolic transformation of the drugs is the critical factor in the drug elimination from the body. One of such metabolic process is glucuronide conjugation in the phase two reaction. Many scientists have shown much interest in discussing the CYP 450 enzymatic metabolism but the glucuronidation conjugation has its own importance in conjugation metabolic reaction. Here we discussed about all the uridine diphosphate glucuronosyl transferase (UGT) isoforms in a detailed way and their location in the various parts of human body. Glucuronidation are observed more frequently in moleculescontaining functional groups like R-COOH, R-OH, R-NH2. Factors like age, gender, diet, smoking and alcohol etc. will affect the glucuronidation conjugation reaction. To assess the glucuronidation products various analysis is done like in-vitro tests of microsomal incubation assays, sub cellular enzymatic assay, liquid chromatography mass spectroscopy, HRMS etc., are carried out. In presence of enzyme inducers and inhibitors, how UGTs will behave is discussed here. Finally, the list of drugs that are undergoing glucuronidation metabolism and their metabolites identification and characterization using chromatographic techniques are mentioned.

Keywords: Glucuronidation, UGT enzymes, HPLC, LC-MS/MS, GC-MS/MS.


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