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 À1 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 mL 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.

Rapid measurement of tacrolimus in whole blood by paper spray-tandem mass spectrometry (PS-MS/MS)

“…An ionization voltage of +3.4 kV was applied, initiating production of analyte ions from the tip of the paper which were drawn directly into the MS inlet. More information about experimental and fundamental details can be found in the literature (8,9,12). MS conditions were optimized using continuous infusion of tacrolimus and SIL-IS solutions into the commercial H-ESI source by a syringe pump, and SRMs for both compounds selected accordingly (Table 1).…”

“…As the solvent wicks through the sample, soluble components are extracted into the solvent, leaving behind the bulk of proteins and lipids [6]. A high voltage (3-5 kV) is applied to the moist paper, and an electrospray is induced at the sharp tip of the triangular shaped paper in the cartridge, which is held stationary in front of the inlet to the MS. As solvent evaporates, gas phase ions of the analyte molecules are generated which can then be detected by MS. PS-MS/MS has been successfully used for quantitative analysis of xenobiotics (8)(9)(10)) and endogenous compounds (11) from whole blood.…”

Ionization Suppression and Recovery in Direct Biofluid Analysis Using Paper Spray Mass Spectrometry

“…Paper spray is a member of this growing cohort of ambient ionization or direct analysis methods that was conceived because of the growing interest in storing and transporting blood samples as dried spots. One of the major applications of paper spray mass spectrometry has been screening and quantitative analysis of drugs and other small molecules from biofluids such as blood, urine, and plasma [3][4][5][6][7][8][9][10][11][12][13][14].…”

Simultaneous monitoring of anesthetics and therapeutic compounds with a portable multichannel potentiostat

“…Currently, the measurement of drugs concentration in blood is performed using techniques such as mass spectrometry [10], liquid or gas chromatography or immunoassay [11]. However, all of them are not technically suitable for portable online continuous monitoring.…”