Characterlstlcs of a technique termed liquid ionization mass spectrometry for organic compounds are described. I n particular the use of additives (solvent, matrix, and reagent) for nonvolatile compounds and ease of sample handling are reported. Metastable argon atoms are used to lonlze compounds at atmospheric pressure. Samples are placed on a needle tip posltloned near an aperture ieadlng to the mass analyzer. The needle Is heated and a hlgh voltage (about 1 kV) is applied to the needle. Mass spectra obtained by this method showed ions characterlstlc of the molecular weight and the structure of the compounds. Liquld aikane(s) is a good matrix for nucleosides, while glycerol Is good for phosphatldyichoilnes. A minute amount of a reagent such as ethanoiamlne Increases the abundance of MH' Ions of sucrose, resulting in reproduclble mass spectra. The use of several reagents (e.g., D,O) for one compound Is suggested in order to obtain additional structural information. The advantages of the method are also described.In recent years, nonvolatile and/or thermally labile organic compounds have been successfully investigated by several soft methods of ionization such as field desorption (FD) ( I ) , laser desorption (2), plasma desorption (3), secondary ion mass spectrometry (SIMS) (4), fast atom bombardment (FAB) (5), atmospheric pressure ionization (API) (6, 7), and direct exposure techniques such as direct CI (8), in-beam E1 and CI (9, lo), emitter CI ( I l ) , and so on. There are, however, many compounds whose mass spectra cannot be obtained satisfactorily by using any of these techniques, especially when such compounds are present in an actual sample. The influence of coexisting compounds has to be investigated not only for obtaining a good mass spectrum of a compound but also for applying the rapidly developing method termed mass spectrometry/mass spectrometry (MS/MS) (12) to nonvolatile compounds.Many efforts to combine a liquid chromatograph with a mass spectrometer (LC/MS) have been made in recent years (6, 13-16) and commercial instruments are now available. There is, however, still difficulty in measuring nonvolatile compounds reliably by LC/MS combinations presently available. Therefore, it is important to understand the mechanism of ionization and desorption (1 7) and the effects of experimental parameters in order to develop new techniques in mass spectrometry.We have developed a method which we call "liquid ionization" (referred to as LI in this paper) for ionizing organic compounds present as a liquid or in aolution at atmospheric pressure (1419). Thus, the method (LI) is a variation of the atmospheric pressure ionization (API) developed by Horning and his co-workers (13). The main differences in the principles of the method (LI) from that of Horning and other API methods (6, 7) involve the technique of ionization and the sample introduction system. There are two techniques of ionization in the LI method, one of which utilizes proton transfer reactions from cluster ions of water, (H20),Ht, to sample mol...