Rapid analysis of whole blood by paper spray mass spectrometry for point-of-care therapeutic drug monitoring

Abstract

Paper spray mass spectrometry is applied to oncology drugs in fresh whole blood samples supported on filter paper substrates instead of dry blood as done previously. Addition of the coagulant alum clotted the blood and allowed for immediate sample analysis. The coagulant did not interfere with the function of the paper spray nor did it add features to the mass spectra. Quantitative analysis of therapeutic drugs in the blood was achieved utilizing internal standards which were pre-spotted onto the filter paper. Eight oncology drugs were examined, with lower limits of detection ranging between 0.5 and 17 ng mL⁻¹ and linear dynamic ranges greater than two orders of magnitude. Inter-day accuracies of quality controls for pazopanib ranged from 102 to 118%, with imprecisions of 9 to 13%. This one-step method requires 10 μL of blood, a drop of solvent, and takes 45 seconds per trial. These results indicate applicability to point-of-care therapeutic drug monitoring in a clinical setting.