Ultrasonication has been used to accelerate chemical reactions. It would be ideal if ultrasonication-assisted chemical reactions could be monitored by suitable detection tools such as mass spectrometry in real time. It would be helpful to clarify reaction intermediates/products and to have a better understanding of reaction mechanism. In this work, we developed a system for ultrasonication-assisted spray ionization mass spectrometry (UASI-MS) with an ~1.7 MHz ultrasonic transducer to monitor chemical reactions in real time. We demonstrated that simply depositing a sample solution on the MHz-based ultrasonic transducer, which was placed in front of the orifice of a mass spectrometer, the analyte signals can be readily detected by the mass spectrometer. Singly and multiply charged ions from small and large molecules, respectively, can be observed in the UASI mass spectra. Furthermore, the ultrasonic transducer used in the UASI setup accelerates the chemical reactions while being monitored via UASI-MS. The feasibility of using this approach for real-time acceleration/monitoring of chemical reactions was demonstrated. The reactions of Girard T reagent and hydroxylamine with steroids were used as the model reactions. Upon the deposition of reactant solutions on the ultrasonic transducer, the intermediate/product ions are readily generated and instantaneously monitored using MS within 1 s. Additionally, we also showed the possibility of using this reactive UASI-MS approach to assist the confirmation of trace steroids from complex urine samples by monitoring the generation of the product ions.

Ultrasonication-assisted spray ionization mass spectrometry (UASI-MS) [1,2] is a recently developed technique. The UASI-MS requires only an inexpensive ultrasonicator and a tapered capillary for the generation of gas-phase ions from liquid samples at atmospheric pressure. No external voltage is connected to the UASI capillary emitter, which is close (~5 mm) to the orifice of a mass spectrometer. Ultrasonication drives the liquid sample from the inlet to the capillary outlet followed by formation of fine droplets, and gas-phase ions are then generated for MS analysis. UASI-MS is suitable for the analysis of a wide mass range of biomolecules, such as amino acids, peptides, and proteins. [1] A notable advantage of coupling UASI for MS analysis is relatively low ion background observed in the UASI mass spectra. In conventional electrospray ionization (ESI) MS, background ions resulting from electrochemical reduction/oxidation of solvent are unavoidable because of the use of high voltages on the sample emitter to generate electrospray. Alternatively, ultrasonication is used to assist the generation of very fine droplets from the outlet of a tapered capillary in the UASI-MS without applying any electric connection in the UASI capillary emitter. The capillary outlet is close to the orifice of the mass spectrometer, which is applied with a high voltage. Thus, we believe that the generated fine droplets are polarized on the way to the orifice of the mass spectrometer. [3] A floating potential was therefore generated. After subsequent solvent evaporation, the polarized droplets shrink followed by disruption because of coulombic repulsion resulting from the increase of the charge density, leading the formation of smaller droplets with net positive charges, neutral state, and net negative charges. The positively charged droplets tend flying to the orifice of the mass spectrometer applied with a negative potential. After desolvation, gas-phase ions are readily formed for MS analysis. Owing to the ease of polarization, the formation of very fine droplets is a prerequisite for successful generation of multiply/singly charged ions when no electrode/voltage is applied on the sample emitter as demonstrated in several reports. [1,2,[4][5][6][7] In the UASI-MS, ultrasonication is significant for the assistance of the formation of fine droplets. The elimination of the use of high voltages in the UASI approach also leads the reduction of background ions. In this work, UASI-MS is further employed for the analysis of saccharides and samples containing high concentrations of salts. The salt effects of UASI-MS are investigated in this study.An ultrasonicator (2.5 l, 160 W, 42 kHz), generally filled with 2.1 l of water, was used in the UASI setup. A capillary was tapered to have a sharp tip. The tapered capillary (length, 20 cm; tip diameter, ca. 10 AE 3 mm) was filled with the sample solution before being placed in an aqueous sample solution within a vial in the ultrasonicator (Fig. 1). The tapered capillary outlet was close (~5 mm) to th...

In this study, we explored a new approach for generating ions of organics and biomolecules using contactless atmospheric pressure ionization (C-API). That is, a tapered capillary (~20 cm) was connected to a syringe, which was coupled to a syringe pump for providing a given flow rate to introduce sample solution to the proximity of a mass spectrometer. The gas phase ions derived from analytes were readily formed in the capillary outlet, which was very close to the mass spectrometer (~1 mm). No external electric connection was applied on the capillary emitter. This setup is very simple, but it can function as an ion source. This approach can be readily used for the analysis of small molecules such as amino acids and large molecules such as peptides and proteins. The limit of the detection of this approach was estimated to be ~10 pM when using bradykinin as the sample. Thus, we believe that this approach should be very useful for being used as an alternative ion source because of its low cost, high sensitivity, simplicity, and ease of operation.

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