Page - (000104) - in Biomedical Chemistry: Current Trends and Developments

are taken in day-to-day laboratory practices, such as various kinds of validation, inclusion of independent quality control (QC) samples or calibration curves mimicking real samples as close as possible. Considering the distinct objectives and techniques employed in each stage of DDD to characterize ADME/pharmacokinetics, it is evident that bioanalysis must be adapted to each particular case, requiring different sample preparation and analytical methodologies which do not need the same quality validation results. Table 2.1.4 suggests the general characteristics of bioanalytical methods and the validation requirements for each DDD stage. In opposition to the regulated bioanalysis, which is focused on the rigorous development and validation of highly specific bioanalytical methods for a selected drug candidate in a particular biological fluid, the most striking feature of discovery bioanalysis is its breadth and diversity of in vitro and in vivo studies. Consequently, a high number of sample matrices are generated and a high number of different NCEs are simultaneously measured. As a result, the throughput, capacity and turnaround requirements are generally much higher in discovery phases in order to make timely decisions and process the elevated number of samples. At this stage, early screening tests conducted in vitro and in vivo can be performed following either good laboratory practices or not, with no real need to input significant resources in an attempt of developing a rugged and fully validated method. Instead, only some parameters, such as accuracy, precision and selectivity must be contained under certain well-accepted boundaries to guarantee that the results can be used for critical decision making. Thus, at drug discovery stages, the ideal bioanalytical assay should be simple, straightforward, rapid, largely applicable, efficient and allow significant throughput in order to be a successful screening tool capable of quantifying several NCEs subjected to the in vitro and in vivo tests performed in initial screening experiments. Table 2.1.4: Bioanalysis and method validation requirements suggested during drug discovery and development.