Miniature Mass Spectrometry for Point-of-Care Testing the GPIIb/IIIa Inhibitor Tirofiban during Perioperative Period of Percutaneous Coronary Intervention

Precise administration of tirofiban must be carefully considered to achieve the best treatment efficacy and maximize safety for patients. Herein, a paper spray ionization (PSI) linear ion trap (LIT) portable mass spectrometer (pMS) based point-of-care testing (POCT) technique was developed for on-site sampling, clinical testing, and immediate analysis of tirofiban blood drug concentrations. The results showed that tirofiban formed a significant and stable parent ion peak at <i>m</i>/<i>z</i> 441.3 by MS1 full scan in positive ion mode, which fragmented into product ions at <i>m</i>/<i>z</i> 395.4, <i>m</i>/<i>z</i> 321.3, <i>m</i>/<i>z</i> 276.3, and <i>m</i>/<i>z</i> 260.3 through collision-induced dissociation (CID) in MS/MS. To improve ion response, the parameters were optimized to the voltages of ionization 3600 V, ion isolation 1 (ISO1) 8 V, ion isolation 2 (ISO2) 2 V, and collision-induced dissociation (CID) 3 V. This method was validated, and the limit of detection (LOD) and limit of quantification (LOQ) were found to be 10.1 and 33.7 μg·L^-1, respectively. For precision, it had the relative standard deviation (RSD) of interday precision of 4.8 to 6.7% and the RSD of intraday precision of 7.8 to 8.3%. The recovery of the method ranged from 87.5 to 93.4%. Although matrix effects in blood samples had some inhibitory effects on the target signal formation, the method compensated for part of the matrix effects by establishing a matrix-matched calibration curve, which exhibited good linearity with a <i>R</i>2 of 0.9987. Finally, the method was applied to the detection of tirofiban in clinically collected blood samples. Out of 12 samples, ten had tirofiban concentrations between 35.4 and 72.1 μg·L^-1 while the remaining two were below the LOQ. The method needs further optimization and validation in the future to improve its sensitivity and stability.