ADMET studies

An important aspect in the drug discovery process is the early assessment of the metabolic stability of molecules, with the structural identification of key metabolites. This information will indicate the most labile substructures and structural modifications necessary to increase the stability of molecules. At the same time, any metabolic activation products can also be identified for early evaluation in terms of efficacy and safety. The research laboratory has a long tradition in this field and has developed analytical expertise for the analysis in various primate and rodent biological matrices, including plasma, skin, liver fractions, reconstructed gastric and intestinal fluids, or extracted and semi-purified from cellular models. The main activities concern the development of methods using liquid chromatography coupled with UV detectors or mass spectrometry (LC-UV and LC-MS/MS) for the qualitative and quantitative analysis of drugs and metabolites in complex matrixes. These methods are applied to identify and characterise metabolites, assess cell toxicity, analyse biological matrices from pharmacokinetic studies in animals and humans or study interactions between drugs and enzyme systems, including activation and inhibition processes of enzymes or hepatic and extrahepatic metabolism.

• Baron G., Altomare A., Regazzoni L., Fumagalli L., Artasensi A., Borghi E., Ottaviano E., Del Bo’ C., Riso P., Allegrini P., Petrangolini G., Morazzoni P., Riva A., Arnoldi L., Carini M., Aldini G. Profiling Vaccinium macrocarpon components and metabolites in human urine and the urine ex-vivo effect on Candida albicans adhesion and biofilm-formation. Biochem Pharmacol. 2020 Mar:173:113726. doi: 10.1016/j.bcp.2019.113726.
• Everaert I., Baron G., Barbaresi S., Gilardoni E., Coppa C., Carini M., Vistoli G., Bex T., Stautemas J., Blancquaert L., Derave W., Aldini G., Regazzoni L. Development and validation of a sensitive LC–MS/MS assay for the quantification of anserine in human plasma and urine and its application to pharmacokinetic study. Amino Acids. 2019 Jan;51(1):103-114. doi: 10.1007/s00726-018-2663-y.
• Baron G., Altomare A., Regazzoni L., Redaelli V., Grandi S., Riva A., Morazzoni P., Mazzolari A., Carini M., Vistoli G., Aldini G. Pharmacokinetic profile of bilberry anthocyanins in rats and the role of glucose transporters: LC–MS/MS and computational studies. J Pharm Biomed Anal. 2017 Sep 10:144:112-121. doi: 10.1016/j.jpba.2017.04.042.