Assessment of Whole Blood Stability and Blood/Plasma Distribution of Drugs

To ensure the reliable determination and rational interpretation of toxicokinetic (TK) and pharmacokinetic (PK) parameters, it is critical to understand the behaviour of a drug and/or drug metabolite(s) in whole blood of the intended species. Of key importance is the stability profile of the analyte of interest in whole blood. There are two main approaches for determining the stability of a drug in blood. The first is to use the plasma derived from blood and the second is simply to use blood as the analytical matrix. An awareness of the advantages and limitations of each approach is important in designing an appropriate stability assessment experiment. Blood/plasma distribution of the drug of interest gives an insight into how the drug interacts with the various components of circulating blood. An understanding of these interactions allows the interpretation of TK/PK parameters with reference to free or total concentrations of drug and enables a rational choice of the primary matrix for bioanalytical investigations.