Stability of Drugs, Drug Candidates, and Metabolites in Blood and Plasma

Abstract Determination of drug or drug metabolite concentrations in biological samples, particularly in serum or plasma, is fundamental to describing the relationships between administered dose, route of administration, and time after dose for achieving the optimal clinical response. While a well‐characterized, accurate analytical method is needed to define these parameters, it must also be established that the analyte concentration in the sample at the time of analysis is identical to the concentration at sample acquisition. This is necessitated by the fact that drugs and their metabolites are susceptible to degradation in samples due to metabolism or to physical and chemical processes, resulting in a lower measured concentration than was in the original sample. Careful examination of analyte stability during processing and storage and, if necessary, adjustment of procedures and conditions to maximize stability, are a critical component of method validation to ensure the accuracy of the data. The protocols provided in this unit address the stability of the analytes in whole blood and blood‐derived samples prior to sample preparation for analysis. Issues addressed include sample acquisition, processing of whole blood, and storage of blood‐derived samples. © 2016 by John Wiley & Sons, Inc.