Continuous synthesis of BaFe 2 O 4 and BaFe 12 O 19 nanoparticles in a droplet microreactor for efficient detection of antihistamine drugs in oral fluid using surface-assisted laser desorption/ionization mass spectrometry

Surface-assisted laser desorption/ionization mass spectrometry (SALDI-MS) has received considerable attention as a complementary approach to matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), offering substantial potential for analyzing molecules in the low-mass region. Herein, we propose a facile method, a microreactor for the synthesis of two types of barium ferrite (BaFe O and BaFe O ) nanoparticles (NPs) within moving droplets for detecting antihistamine (AH) drugs in oral fluid (OF). The synthesized BaFe O and BaFe O NPs exhibited small particle size, good ultraviolet absorption, and excellent performance in SALDI-MS, as determined by survival yield measurements. The limits-of-detection for AH drugs were in the range of 1 pg mL to 100 ng mL , and spot-spot reproducibility of the SALDI substrates was satisfactory. Moreover, when analyzing cetirizine in OF, the obtained recoveries of cetirizine were 101% and 99% using BaFe O and BaFe O NP, respectively. Furthermore, the proposed method was validated by analyzing OF samples from a healthy volunteer who consumed a 5 mg levocetirizine tablet for seven days. SALDI-MS analysis confirmed the successful detection of endogenous components, the parent ion of cetirizine, and other exogenous substances. This study reports an advanced application of droplet microreactor technology for designing and synthesizing a wide range of novel and efficient SALDI-MS substrates for various applications.