Hematocrit prediction in volumetric absorptive microsamples

•Volumetric absorptive microsampling (VAMS) allows to collect a fixed volume of blood.•The hematocrit (HT) may impact recovery and the VAMS/plasma concentration ratio.•Two methods were developed to estimate the HT based on a VAMS’ potassium content.•The procedures are compatible with an LC–MS workflow.•Application to patient samples yielded good results. Recently, volumetric absorptive microsampling (VAMS) has been suggested as an alternative to DBS sampling. With VAMS, a fixed volume of blood (approximately 10 μL) is wicked up by the absorbent tip of a collection device, independent of the hematocrit (HT) of the blood sample. This way, VAMS effectively avoids the HT bias which occurs in partial-punch DBS analysis. Nonetheless, the HT remains an important variable in VAMS analysis, particularly if VAMS-based blood results need to be converted to serum or plasma values to allow comparison with e.g. plasma-based therapeutic intervals. Indeed, an analyte’s plasma to whole blood ratio may be HT-dependent. Therefore, we developed two straightforward methods to derive the HT value from a VAMS sample based on its potassium content. One of these methods uses an aqueous extraction procedure, whereas the other one requires an organic extraction. Both methods have the potential to be seamlessly integrated with most existing VAMS analyses, allowing both target analyte quantitation and potassium analysis on a single VAMS extract.