Microwave Plasma Torch Mass Spectrometry For The Analysis Of Pharmaceutical Molecules

The emerging of ambient mass spectrometry(AMS)enables the eco-friendly,in situ,real-time,online,high throughput direct analysis of analytes in complex matrix.In recent years,ambient mass spectrometry technology has received a rapid development.Microwave plasma torch mass spectrometry(MPT-MS)is one of the AMS techniques that has been developed in recent years with the advantages of simple operation,no solvent pollution,no electrode contamination,high desorption and ionization ability and fast analysis.MPT has been successfully applied to the analysis of various forms of samples including solid,liquid and gas.MPT-MS has been widely used in food and medicine,environmental monitoring,public safety,and other fields like mineral resource analysis,clinical diagnosis.This dissertation mainly performs the application of microwave plasma torch mass spectrometry in drug molecular analysis including the following four aspects:1.Rapid identification of active ingredients in tablets by MPT-MSMicrowave plasma torch has the feature of flexible and adjustable microwave power,which makes MPT have both soft and hard ionization properties.The active ingredients in both unilateral and compound preparations were rapidly identified by obtaining the quasi-molecular ion and its fragment ions corresponding to the MS~n(n≥2)ions in the MPT-MS full-scan mass spectra.It could be identified that these ions were the fragment ions of protonated drug molecules rather than the matrix material in the tablet.In addition,the qualitative and semi-quantitative analysis of active ingredients in acetaminophen tablets were achieved by coupling MPT with quadrupole mass spectrometer which has no tandem MS function.Therefore,MPT-MS could be a powerful analytical platform for the rapid identification of active ingredients in tablets without sample pretreatment and tandem mass spectrometry,which makes MPT a promising device in the miniaturization of mass spectrometer.2.Photo-Thermal Stability Sequencing of pharmaceutical molecules by MPT-MS(1)A versatile platform of microwave plasma torch(MPT)mass spectrometry has been developed for rapid photo-thermal stability analysis of pharmaceutical samples without sample pretreatment owing to the moderate temperature and light irradiation of MPT.As the demonstration,the relative stabilities of the 6 pharmaceuticals were rapidly sequenced as chlorpheniramine<metronidazole<ornidazole<acetaminophen<tinidazole<theophylline within a few minutes using the MPT-MS data.Informative fragment ions of the pharmaceutical quasi-molecular ions were observed with a relatively high MPT power,revealing the chemical mechanism of the degradation and detecting the light irradiation-induced dissociation pathways.(2)The isomers of xylene were successfully differentiated,showing that MPT-MS resolved the energy difference in a narrow scale.The experimental data demonstrated that MPT-MS could be a useful platform for the rapid analysis of photo-thermal stability of drug candidates,providing in-depth characterization on the molecular stability and degradation mechanism with the fastest analysis speed and least sample consumption.3.Fragmentation mechanism of pharmaceutical molecules by MPT-MSThe fragmentation mechanism by MPT-MS of nitroimidazoles including metronidazole and ornidazole,xanthine compounds including theophylline,theobromine,caffeine,as well as acetaminophen were studied,which was beneficial to further understand the structure-activity relationship of pharmaceutical molecules as well as the relationship between the pharmaceutical structures and the MS fragmentation pathways.In addition,the fragmentation mechanism of xylene isomers by MPT-MS was also studied.4.An amantadine advanced complex structure catalyzed by MPT-MS(1)Amantadine hydrochloride tablets were directly sampled by MPT-MS and the ion at m/z 244 was found to be the base peak at high microwave power.It could be inferred that amantadine was catalyzed by MPT,forming an advanced complex structure.(2)The successful detection of the ion at m/z 244 by ESI-MS proved that the catalyzed product existed in the powder produced during MPT-MS sampling.And the suction machine was the preferable collecting method.The experimental results showed that the amantadine molecules were catalyzed and the corresponding synthesized product has the stability to light,electron,heat and alcohol,which extends the application of MPT-MS in the field of catalyzed synthesis.