Page - (000085) - in Biomedical Chemistry: Current Trends and Developments

lead compound fails in vivo because, for instance, it is so short-lived that its clinical benefits would be minimal. In fact, since the pharmaceutical industries embraced the early pharmacokinetic screening of drug candidates, the attrition rates of DDD were substantially improved and, therefore, it is currently straightforward to make a decision on the pharmacokinetic desirability of each drug candidate in the beginning of DDD processes and not only later in the non-clinical and clinical development stages (Saxena, 2008; Gallo, 2010). This demand expanded the investigation on pharmacokinetics into the initial phases of drug discovery and several in silico, in vitro and in vivo models have been developed and improved to optimize the pharmacokinetic behavior of drug candidates at different stages of DDD. Moreover, pharmacokinetic principles are also applied during the post approval period of a drug, particularly for therapeutic drug monitoring (which has recently been defined as therapeutic drug management, TDM), evaluation of line- extension medicinal products and generic formulations, particularly through bioavailability/bioequivalence (BA/BE) studies. Taking into account these new attempts, a close involvement between pharmacokinetics and bioanalysis (defined as the determination of drug concentrations on biological specimens) became required in order to obtain data with a high quality level and allow an adequate interpretation and ultimately rational decision-making. On the other hand, the increasing number of NCEs that must be investigated and the application of pharmacokinetic screening at initial phases of DDD increases the number of samples that must be analyzed and, consequently, new bioanalytical techniques with higher sensitivity, selectivity and speed have emerged. Indeed, decades ago, high performance liquid chromatography (HPLC) coupled with ultraviolet (UV) or fluorescence detection and gas chromatography (GC) with mass spectrometry (MS) ensured the acquisition of plasma concentration data to define drug exposure in animal tests and clinical studies. In current practices, liquid chromatography (LC) coupled to MS or tandem mass spectrometry (MS/MS) are becoming essential due to their higher throughput capacity to identify and quantify the parent drugs and metabolites in biological matrices, enabling fast and effective decision- making. Furthermore, new strategies for sample preparation have also