K.L. Busch

Matrix effects, internal energies and MS/MS spectra of molecular ions sputtered from surfaces

Desorption ionization (DI) involves the transfer of material from a condensed phase to a collision-free environment (ref. 1,2). Tandem mass spectrometry (ref. 3), used with desorption ionization, improves the signal-to-noise ratio for spectra of individual analytes present in complex matrices, provides evidence that fragmentation in DI is typically due to gas phase dissociations of energized but intact molecular ions after they have left the surface, and allows the compositions of desorbed ions to be characterized. A complementary approach to improving analytical performance and obtaining further information on the species and processes of desorption ionization is to be found in the examination of the sample in the presence of matrix materials. Some matrices act as reagents which yield an appropriate ionized form of the analyte (ref. 4), either during or prior to energization of the sample, while others serve to isolate analyte molecules and reduce intermolecular analyte reactions (ref. 5). Particularly complex matrices are those encountered when examining samples directly from chromatographic materials or in their natural state, for example, crude extracts of plant materials. Examples of analyses in these situations are given. n nAmmonium chloride acts as a valuable matrix material which, even at sample dilutions of 103, can cause an increase in both absolute secondary ion yields and in spectral persistence (ref. 6,7,8). This matrix has beneficial effects in SIMS, FAB and LD mass spectra and has the advantage of being totally transparent except under high flux conditions. It is shown to decrease ion internal energies, presumably by providing a sputtered ion with a shield of solvating molecules which are readily lost as NH3 and HCl, thereby carrying away excess energy. Cluster ions [(NH4)n+1Cln]+ are observed in FAB and shown by MS/MS to undergo ready desolvation. These cluster ions are remarkable for the absence or low intensity of clusters where the total number of anions and cations is a prime number and for the high intensity of clusters which may be made up of regular arrays of atoms, e.g., 3×3×3 or 3×3×5. n nA qualitative model of desorption ionization, advanced some years ago (ref. 9), accommodates the observations reported here using MS/MS and matrix effects. The chief features of this model are (i) isomerization (loss of identity) of the input energy, (ii) desorption of preformed ions or intact molecules, (iii) ion/molecule reactions such as cationization occurring in the selvedge region, (iv) dissociation of energetic (metastable) ions well-removed from the surface. In most cases just a few types of ionic species are sputtered from the surface and their unimolecular chemistry determines the chief features of the desorption ionization mass spectrum.

Desorption ionization mass spectrometry: Secondary ion mass spectra of phosphonium salts

Abstract Secondary ion mass spectra are obtained for involatile phosphonium salts not analyzable by conventional ionization methods. The spectra typically exhibit an abundant intact cation and fragment ions which result from predictable losses of stable neutral species from the cation. A systematic pattern of fragmentation occurs in simple salts which serve as model compounds, and also more complex structures which are of pharmaceutical interest. Close parallels with the behavior of related volatile compounds in electron and chemical ionization mass spectrometry are observed in the presence of characteristic fragment ions and a tendency for rearrangement with elimination of stable molecules. Doubly charged salts undergo loss of a charged fragment such as a proton to give stable singly charged species. Sensitivity is such that a few nanograms of phosphonium salt suffices to provide a spectrum observable for ten to twenty minutes. The preferential desorption of precharged species makes possible the direct analysis of these salts in Chromatographic media, including electrophoresis membranes, and also the direct desorption of these salts from vacuum compatible solutions.

Enhanced ionization of organic salts in secondary-ion mass spectrometry

Abstract Ammonium chloride increases the absolute signal intensity for the intact cations of organic ammonium, pyrylium and phosphonium salts when admixed in 10−10 3 -fold excess. This signal enhancement results in improved signal-to-noise ratios and is achieved without addition of extraneous ions to the spectrum. The ionization efficiency (secondary ions produced per incident primary ion) is similar for neat and ammonium chloride diluted samples. However, the ionization yield (secondary ions produced per sample molecule) is enhanced by the matrix by four orders of magnitude. Sensitivity, calculated here for a desorption ionization method, is 0.5−1 × 10 −10 C μg −1 , and is less than that of electron ionization and chemical ionization sources. Spectra of submicrogram amounts of organic species in ammonium chloride are stable and can be recorded continuously for many hours, as compared to less than an hour for the neat compounds. Even subnanogram amounts of sample diluted in ammonium chloride give spectra which last a number of minutes. Matrix-diluted samples may be withdrawn from the spectrometer and stored for days before being reanalyzed without incident. With this matrix, the technique is essentially nondestructive. Total ionization yields for matrix-diluted samples are estimated at 0.01-0.1%. Primary-ion fluxes impinging on matrix-diluted samples exceed static SIMS limits without evidence of beam damage.

Surface modification by soft landing of reagent beams

Abstract Unusual ionic species created in mass spectrometry can be separated from their congeners, isotopically selected, and supplied with well-defined translational energies. Such advantages of precise characterization counterbalance the disadvantage of small ion flux in synthetic experiments which capture these reagents at surfaces, and analyze the products by sensitive surface analytical techniques. Variation of the energy of the transferred ions is reflected in the products formed at the secondary surface. Preparation times of one hour create sufficient material for analysis by SIMS.

Secondary ion mass spectra of quaternary pyridine aldoximes

Abstract The secondary ion mass spectra (s.i.m.s.) of the most widely used therapeutic monoquaternary pyridine aldoximes and diquaternary pyridine aldoximes, as well as some related monoquaternary ammonium salts and neutral oximes, are reported. The monoquaternary derivatives of the oximes yield prominent intact cations which provide molecular weights, and fragmentation patterns which are dominated by even-electron ions. The diquaternary oximes investigated do not give dications, but rather undergo charge separation reactions sometimes accompanied by intramolecular aromatic substitution, and they sometimes yield monoquaternaries by expulsion of a proton. The s.i. mass spectra are structure-specific for the monoquaternary salts, allowing isomer distinction in the cases examined. Quaternary salts can be quantified by s.i.m.s., and low detection limits (less than 50 ng) are demonstrated here for the oxime salts; thus s.i.m.s. is an appropriate analytical technique for the title compounds. Procedures of derivatization which convert the neutral amines to ionic compounds, such as quaternization with alkyl halides, provide a simple means of obtaining high-quality s.i.m.s.

Charge exchange using a double quadrupole mass spectrometer

Abstract Charge exchange mass spectra obtained on a double quadrupole (QQ) mass spectrometer are compared with those obtained by other methods. The effects of reagent ion recombination energies and of axial ion translational energy on these spectra are followed.

Matrix Effects on Internal Energy in Desorption Ionization

Desorption ionization (DI) mass spectrometry encompasses a family of techniques in which energization of a condensed phase leads to ejection of ions into the vacuum with subsequent mass analysis and detection [1]. In contrast to the gas—phase ionization methods of electron, chemical, and photo- ionization, DI techniques are by their nature sensitive to the physical and chemical nature of the matrix from which the ions are ejected. Success in the analysis of nonvolatile and thermally fragile molecules has been enough to thrust these techniques into routine use in just a few years. DI spectra of pure compounds can often be interpreted in terms of known gas—phase ion chemistry. This provides evidence for the desorption, from the surface, of intact ions with some degree of internal excitation; the fragmentation processes undergone are then defined by the nature and the amount of the internal energy. Since the ion is in an isolated state, fragmentation processes should be the same as those undergone by ions of the same structure formed directly in the gas phase by chemical ionization [2]. MS/MS experiments have confirmed this premise for particular DI conditions. Ions are isolated by a first stage of mass analysis, and then activated by collision. The masses and relative abundances of the resultant fragment ions (determined by the second stage of mass analysis) match those of the DI spectra. Metastable ion transitions have also been directly observed in DI spectra.

Secondary Ion Mass Spectra (SIMS) as a Tool for Biomedical Studies: Mono- and Diquaternary Pyridine Oximes

Secondary Ion Mass Spectrometry (SIMS) was originally developed for study of metal surfaces and other involatile inorganic materials by sputtering. In recent years SIMS has been established as an excellent method for the study of non-volatile organic compounds (Day 1980). It is especially useful for analysis of onium salts in neat form and in biological matrices as well (Unger et al. 1980, 1981). Organic SIMS may in fact be more convenient than field desorption for such applications. The usefulness of the technique is demonstrated by examples from the study of mono- and diquaternary pyridine aldoximes that are of long standing clinical use as antidotes for organophosphorus pesticide intoxications in humans. Compounds such as N-methylpyridine-2-aldoxime iodide give an abundant intact cation and structurally diagnostic fragmentation thereof. This enables differentiation of structural and positional isomers. Tertiary oximes, giving poor spectra can be studied successfully after in situ quaternization (Busch et al. 1982). Diquaternary oximes like toxogonin and TMB-4 were also investigated and useful spectra were obtained. The technique is amenable for quantitation of such agents given the requisite dueterated standards.