Critical considerations of matrix selection in LC–MS bioanalysis for toxicokinetic and pharmacokinetic assessment in drug development
Fu Y, Li W & Flarakos J | Bioanalysis, 13(8), 605-608, (2021)
Keywords: • bioanalysis • blood/plasma distribution • blood stability • matrix selection • plasma • protein binding • stability • whole blood
In drug development, plasma rather than whole blood has been the primary biological matrix for the toxicokinetic (TK) or pharmacokinetic (PK) assessment of drug candidates [1,2]. The preference in using plasma over blood in these assessments is not only owing to the homogeneous nature of plasma, but also, more importantly, due to the fact that plasma concentration is generally more relevant than blood to the effect of the drug [3]. In contrast, blood is more suitable than plasma for monitoring drugs that bind or sequestrate to erythrocytes and/or show temperature dependence or nonlinear blood-to-plasma distribution [4–6]. From the 3R (replacement, refinement and reduction) and patient centric perspectives, collecting small volumes of blood via dried blood spot sampling or volumetric absorptive microsampling has demonstrated profound advantages over plasma sample collection for drug monitoring. These advantages include but are not limited to smaller sample volume and simpler sample collection and storage, along with improved analyte stability [7,8]. Currently, there are no specific guidelines on biological matrix selection for TK/PK assessment of drugs. Therefore, it is imperative to understand the implications associated with matrix selection and what should be done in bioanalysis to facilitate such a selection.
