Shefali R Patel
2019
Citations
0
Influential Citations
10
Citations
Quality indicators
Journal
Biomedical chromatography : BMC
Abstract
Bioanalysis of unstable compounds such as acyl glucuronide metabolites represents a great analytical challenge due to poor analyte stability in biological matrices. The primary goal for bioanalytical assay development is to minimize the breakdown of acyl glucuronide metabolite into its parent aglycone during sample collection, transportation, storage, and analysis. Samples need to be stabilized ex vivo immediately after sample collection to minimize potential breakdown and thus to ensure accurate concentration measurement of both acyl glucuronide metabolite and its parent aglycone. In this review paper, formation of acyl glucuronide metabolites, importance of establishment of acyl glucuronide exposure measurement and safety coverage, optimization of sample pretreatment to stabilize the acyl glucuronide metabolites, current analytical strategy of assaying them as well as considerations for regulatory filings are discussed. It is important to identify acyl glucuronide metabolites that are capable of undergoing hydrolysis, pH- dependent intra-molecular migration as well as covalently binding to plasma and tissues proteins which can cause toxicity invivo in early stages of drug development. Carefully planning analytical experiments, identifying structures of acyl glucuronides and monitoring their concentrations in early drug development can help assess the risks associated with their exposures and potentially predict their concentrations in the human circulation.