Understanding how the ions work in MPTDI can be used to explore possible reactions in the gas phase and will be very helpful for researchers involved in the analysis or structural elucidation of compounds. During the Ar-MPTDI process, both protonated molecular ions and molecular ions of the analytes are observed (Figure 5). In Figure 5a, the base peak at m/z 750 corresponds to the protonated molecular ion of azithromycin. In addition, a relatively low-abundance molecular ion peak at m/z 749 is also detected. Similarly, both protonated molecular ions and molecular ions are observed in the full mass spectra of oxytetracycline (Figure 5b, m/z 461 and 460), isoniazid (Figure 5d, m/z 138 and 137), ribavirin (Figure 5e, m/z 245 and 244), acetaminophen (Supplementary Figure S-3g, m/z 152 and 151), salbutamol (Supplementary Figure S-3i, m/z 240 and 239), and theophylline (Supplementary Figure S-3j, m/z 181 and 180). It is speculated that these ions are generated by the reactions of Penning ionization (formation of molecular ions) and proton transfer (formation of protonated molecular ions). In the Ar-MPTDI process, Penning ionization ensues under an ultimate working condition of MPT, and molecular ions are generated by a cascade of gas-phase reactions. During the Penning ionization, the high densities of metastable argon (Arm) atom [ionization energy (IE), 11.55 eV for the 3P2 state and 11.72 eV for the 3P0 state]  can ionize these investigated analyte molecules. The proposed reactions caused by metastable argon atoms are listed as reactions 1–3 in Scheme 1. They can take place since the energy of Arm is greater than the first or second ionization energy of analyte (M), Em(Ar) ≥ Eion(M). Reaction 1 is often followed by ion excitation (reaction 2). Reactions 2 and 3 involve direct excitation by metastable argon, and a more rigorous condition is required for the occurrence of reaction 2, Em(Ar) = Eexc(M). Excited species with high excitation energies in the microwave plasma reacting with analyte molecules can generate molecular ions (reactions 4 and 5). Free electrons with high kinetic energy colliding inelastically with gas atoms in plasma and analyte molecules in the sample  is another reason for the generation of analyte molecular ions (reactions 6–8). These reactions are similar to those that happen in microwave-induced plasma (MIP) [45–48]. The protonated molecular ions are produced by proton transfer reaction, which is a dominant reaction in the MPTDI process. The proton affinity (PA) of water is 165 Kcal·mol−1, higher than that of hydroxyl radical (PAOH• = 142 Kcal·mol−1) , so the proton transfer reaction between water and water molecular ion can occur, as shown in reaction 9. The protonated molecular ions [M + H]+ generated by proton transfer were observed because the analyte molecular ion M has a higher proton affinity (PAs of nitrogenous compounds are 200–240 kcal·mol−1 ) than the ionized water clusters (reaction 10). Although the molecular ions are also observed, the signal intensities are not high (Figure 5a, b, d, and e). They even disappear in MPTDI mass spectra of metronidazole (Figure 5c), acyclovir (Figure 5f), and amantadine (Supplementary Figure S-3h). Owing to the high PA of nitrogen atom and the relatively high PA of carbonyl oxygen, the added proton is initially located at them, and these analytes prefer to form protonated molecular ions with relatively high signal intensities during ionization. Thus, molecular ions are observed with low signal intensities or they disappear. The MS data in Figure 5 and Supplementary Figure S-3 confirms the reaction mechanism in MPTDI process proposed in Scheme 1.Scheme 1Probable Reaction Occurring in Ar-MPT. Arm, the metastable states of argon; Em(Ar), the metastable energy of Ar; Eion(M), the ionization energy of M; Eexc(M), the excitation energy of M; PA, proton affinity