Influence of ZnO morphology on the capability of portable paper-based electrospray ionization mass spectrometry to determine therapeutic drugs in complex matrices

Adsorbents play a significant role in enhancing the analytical sensitivity of target analytes in complex samples by mitigating matrix effects. In our recent report, ZnO stood out among various adsorbents to determine target therapeutic drugs in complex biological matrices when applied for portable paper-based electrospray ionization mass spectrometry (PPESI-MS). However, the influence of the morphology of ZnO on the performance of PPESI-MS is elusive. Herein, different morphologies of ZnO particles were prepared via co-precipitation or ultrasonic methods, and their capability to determine different therapeutic drugs in serum were systemically investigated. The results demonstrated that flower-shaped ZnO gave a superior capacity, and its analysis sensitivity was 2.9-12.8-fold higher than those achieved with other ZnO morphologies. Further characterization revealed that the unique performance of flower-shaped ZnO was closely associated with its favorable desorption behavior to drugs, small spray plume, and few spray emitters at the tip of coated paper substrate. To illustrate the potential of flower-shaped ZnO, its coated paper was used as a substrate for the determination of various drugs in complex matrices such as serum, and a limit of detection as low as 2 pg mL-1 was achieved. The corresponding recoveries ranged from 93.2% to 107.2%. The developed protocol is promising in high-sensitivity analysis of target drugs in complex sample matrices. In this study, PPESI-MS was used to demonstrate the effect of different morphologies of zinc oxide on the analytical sensitivity of drugs in complex samples. Among them, flower-like zinc oxide prepared using ultrasonic technique exhibited a superior analytical performance compared to other morphologies.image