Theophylline (MW 180.16) has direct effect on relaxation of airway smooth muscle, and is the drugs for bronchial asthma, asthmatic bronchitis, and other respiratory diseases. In the full-scan mass spectrum of theophylline obtained by MPTDI-TOF MS, the protonated molecular ion at m/z 181 and fragment ions at m/z 124, and 96 can be found (Supplementary Figure S-3j). The result is consistent with the MSn data obtained by MPT-LTQ MS (Supplementary Figure S-1j) and reported in the literature. ISD fragmentation pathway of theophylline is proposed as depicted in Supplementary Figure S-2j. Six-membered ring of protonated theophylline can be opened under high energy, and thus loss of the CONCH3 group from protonated theophylline leads to the observation of the fragment ion at m/z 124, followed by the generation of the ion at m/z 96 by further loss of the CO molecule from the ion at m/z 124.