Page - (000125) - in Biomedical Chemistry: Current Trends and Developments

Current discovery and development programs of new drugs promote pharmacokinetic analysis with in vitro techniques from the earliest stages and throughout preclinical and clinical stages. Thus, the quantification of the parent compound and its main metabolites, as well as the identification of the major metabolites in buffers and biological samples become essential and may determine the success of a developing drug. The introduction of advanced analytical technologies with improved sensitivity and selectivity has opened new frontiers in obtaining pharmacokinetic information with higher accuracy and speed. Conventional HPLC techniques particularly when coupled to mass spectrometry detection (MS or MS/MS) have been successfully employed over the last decade for drug metabolism and clinical investigations. Bioanalysis should not be performed blindly and the analytical methods need to be subject to appropriate method validation depending on the DDD stages. The development and validation of sound bioanalytical methods to support the DDD process is paramount to produce high- quality data, contributing for a reliable interpretation of pharmacokinetics. References Alves, G., Fortuna, A., Falcão, A. (2008) High Performance Liquid Chromatography and its Impact in the Development of Chiral Drugs: a Review. Trends in Chromatography, 4, 1-10. Almeida, L., Potgieter, J.H., Maia, J., Potgieter, M.A., Mota, F., Soares-da-Silva, P., (2008) Pharmacokinetics of eslicarbazepine acetate in patients with moderate hepatic impairment. European Journal of Clinical Pharmacology, 64(3), 267-273. Amore, B.M., Gibbs, J.P., Emery, M.G., (2010) Application of In Vivo Animal Models to Characterize the Pharmacokinetic and Pharmacodynamic Properties of Drug Candidates in Discovery Settings. Combinatorial Chemistry & High Throughput Screening, 13(2), 207-218. Balani, S.K., Miwa, G.T., Gan, L.S, Wu, J.T., Lee, F.W., (2005) Strategy of Utilizing In Vitro and In Vivo ADME Tools for Lead Optimization and Drug Candidate Selection. Current Topics in Medicinal Chemistry, 5(11), 1033-1038. Belka, M., Hewelt-Belka, W., Sławiński, J., Bączek, T., (2014) Mass Spectrometry Based Identification of Geometric Isomers during Metabolic Stability Study of a New Cytotoxic Sulfonamide Derivatives Supported by Quantitative Structure-Retention Relationships. PLoS One, 9(6), e98096. Bhogal, N., Balls, M. (2008) Translation of New Technologies: From Basic Research to Drug Discovery and Development. Current Drug Discovery Technologies, 5(3), 250-262. Boer, de T., Meulman, E., Meijering, H., Wieling, J., Dogterom, P., Lass, H., (2012) Development