Seite - (000105) - in Biomedical Chemistry: Current Trends and Developments

Caco-2, human colon adenocarcinoma cell line; LLOQ, lower limit of quantification; LOD, limit of detection; PAMPA, parallel artificial membrane permeability assay; ULOQ, upper limit of quantification. As the drug candidate enters to the development stages, matrix complexity increases as well as the rigor needed to accurately quantify the NCEs in biological samples and then estimate the pharmacokinetic parameters. The throughput of the method may decrease, but the quality of data must be higher and validation should be formalized and mandated as per the required norms. The most widely accepted guidelines for validation of bioanalytical methods, particularly in the pharmaceutical and medical sciences, are the Technical Requirements for Registration of Pharmaceuticals for Human Use guideline Q2(R1) issued by the ICH (2005), the Guidance for Industry, Bioanalytical Method Validation by the FDA (2001) and the Guideline on Bioanalytical Method Validation recently issued by the European Medicines Agency (EMA) in 2011. Typical validation parameters and the requirements of each guideline are presented in Table 2.1.5. Selectivity is referred to as the ability of a bioanalytical method to unequivocally differentiate and quantify the analytes of interest in the presence of other sample components. Endogenous matrix components, metabolites, and