Rapid detection of drugs in biofluids using atmospheric pressure chemi/chemical ionization mass spectrometry

We have demonstrated that, with simple pH adjustment, volatile drugs such as methamphetamine, amphetamine, 3,4‐methylenedioxymethamphetamine (MDMA), ketamine, and valproic acid could be analyzed rapidly from raw biofluid samples (e.g. urine and serum) without dilution, or extraction, using atmospheric pressure ionization. The ion source was a variant type of atmospheric pressure chemical ionization (APCI) that used a dielectric barrier discharge (DBD) to generate the metastable helium gas and reagent ions. The sample solution was loaded in a disposable glass pipette, and the volatile compounds were purged by nitrogen gas to be reacted with the metastable helium gas. The electrodes of the DBD were arranged in such a way that the generated glow discharge was confined within the discharge tube and was not exposed to the analytes. A needle held at 100–500 V was placed between the ion‐sampling orifice and the discharge tube to guide the analyte ions into the mass spectrometer. After pH adjustment of the biofluid sample, the amphiphilic drugs were in the form of a water‐insoluble oil, which could be concentrated on the liquid surface. By gentle heating of the sample to increase the evaporation rate, rapid and sensitive detection of these drugs in raw urine and serum samples could be achieved in less than 2 min for each sample. Copyright © 2009 John Wiley & Sons, Ltd.     

Direct profiling of phytochemicals in tulip tissues and in vivo monitoring of the change of carbohydrate content in tulip bulbs by probe electrospray ionization mass spectrometry

Probe electrospray ionization (PESI) is a recently developed ESI-based ionization technique which generates electrospray from the tip of a solid needle. In this study, we have applied PESI interfaced with a time of flight mass spectrometer (TOF-MS) for direct profiling of phytochemicals in a section of a tulip bulb in different regions, including basal plate, outer and inner rims of scale, flower bud and foliage leaves. Different parts of tulip petals and leaves have also been investigated. Carbohydrates, amino acids and other phytochemicals were detected. A series of in vivo PESI-MS experiments were carried out on the second outermost scales of four living tulip bulbs to monitoring the change of carbohydrate content during the first week of initial growth. The breakdown of carbohydrates was observed which was in accordance with previous reports achieved by other techniques. This study has indicated that PESI-MS can be used for rapid and direct analysis of phytochemicals in living biological systems with advantages of low sample consumption and little sample preparation. Therefore, PESI-MS can be a new choice for direct analysis/profiling of bioactive compounds or monitoring metabolic changes in living biological systems.     

Ambient imaging mass spectrometry by electrospray ionization using solid needle as sampling probe

Although being an atmospheric pressure ion source, electrospray ionization (ESI) has rarely been used directly for ambient imaging mass spectrometry because the sample has to be introduced as liquid solution through the capillary. Instead of capillary, probe electrospray ionization (PESI), which has been developed recently, uses a solid needle as the sampling probe, as well as the electrospray emitter, and has been applied not only for liquid solutions but also for the direct sampling on wet samples. Biological tissues are composed of cells that contain 70–90% water, and when the surface is probed by the needle tip, the biological fluid adhering to the needle can be electrosprayed directly or assisted by additional solvent added onto the needle surface. Here, we demonstrate ambient imaging mass spectrometry of mouse brain section using PESI, incorporated with an auxiliary heated capillary sprayer. The solvent vapor generated from the sprayer condensed on the needle tip, re‐dissolving the adhered sample, and at the same time, providing an indirect means for needle cleaning. The histological sections were prepared by fixation using paraformaldehyde, and the spatial analysis was automated by maintaining an equal sampling depth into the sample in addition to raster scan. Phospholipids and galactosylceramides were readily detected from the mouse brain section in the positive ion mode, and were mapped with 60 µm lateral resolution to form mass spectrometric images. Copyright © 2009 John Wiley & Sons, Ltd.     

The analysis of industrial synthetic polymers by electrospray droplet impact/secondary ion mass spectrometry

Electrospray droplet impact (EDI)/secondary ion mass spectrometry (SIMS) is a new desorption/ionization technique for mass spectrometry in which highly charged water clusters produced from the atmospheric‐pressure electrospray are accelerated in vacuum by several kV and impact the sample deposited on the metal substrate. In this study, several industrial synthetic polymers, e.g. polystyrene (PS) and polyethylene glycol (PEG) were analyzed by EDI/SIMS mass spectrometry. For higher molecular weight analytes, e.g. PS4000 and PEG4600, EDI/SIMS mass spectra could be obtained when cationization salts are added. For the polymers of lower molecular weights, e.g. PEG300 and PEG600, they could be readily detected as protonated ions without the addition of cationization agents. Anionized PS was also observed in the negative ion mode of operation when acetic acid was added to the charged droplet. Compared to matrix‐assisted laser desorption/ionization (MALDI), ion signal distribution with lower background signals could be obtained particularly for the low‐molecular weight polymers. Copyright © 2009 John Wiley & Sons, Ltd.     

Pressure-dependent electronic structures in multiferroic DyMnO(3): A combined lifetime-broadening-suppressed x-ray absorption spectroscopy and ab initio electronic structure study

Variations in the electronic structure and structural distortion in multiferroic DyMnO(3) were probed by synchrotron x-ray diffraction, lifetime-broadening-suppressed x-ray absorption spectroscopy (XAS), and ab initio electronic structure calculations. The refined x-ray diffraction data enabled an observation of a diminished local Jahn-Teller distortion of Mn sites within MnO(6) octahedra in DyMnO(3) on applying the hydrostatic pressure. The intensity of the white line in Mn K-edge x-ray absorption spectra of DyMnO(3) progressively increased with the increasing pressure. With the increasing hydrostatic pressure, the absorption threshold of an Mn K-edge spectra of DyMnO(3) shifted toward a greater energy, whereas the pre-edge line slightly shifted to a smaller energy. We provide the spectral evidence for the pressure-induced bandwidth broadening for manganites. The intensity enhancement of the white line in Mn K-edge spectra is attributed to a diminished Jahn-Teller distortion of MnO(6) octahedra in compressed DyMnO(3). A comparison of the pressure-dependent XAS spectra with the ab initio electronic structure calculations and full calculations of multiple scattering using the code FDMNES shows the satisfactory agreement between experimental and calculated Mn K-edge spectra.     

Analysis of Renal Cell Carcinoma as a First Step for Developing Mass Spectrometry-Based Diagnostics

Immediate diagnosis of human specimen is an essential prerequisites in medical routines. This study aimed to establish a novel cancer diagnostics system based on probe electrospray ionization-mass spectrometry (PESI-MS) combined with statistical data processing. PESI-MS uses a very fine acupuncture needle as a probe for sampling as well as for ionization. To demonstrate the applicability of PESI-MS for cancer diagnosis, we analyzed nine cases of clear cell renal cell carcinoma (ccRCC) by PESI-MS and processed the data by principal components analysis (PCA). Our system successfully delineated the differences in lipid composition between non-cancerous and cancerous regions. In this case, triacylglycerol (TAG) was reproducibly detected in the cancerous tissue of nine different individuals, the result being consistent with well-known profiles of ccRCC. Moreover, this system enabled us to detect the boundaries of cancerous regions based on the expression of TAG. These results strongly suggest that PESI-MS will be applicable to cancer diagnosis, especially when the number of data is augmented.     

Mass spectrometry of rhenium complexes: a comparative study by using LDI-MS, MALDI-MS, PESI-MS and ESI-MS

A group of rhenium (I) complexes including in their structure ligands such as CF(3)SO(3)-, CH(3)CO(2)-, CO, 2,2'-bipyridine, dipyridil[3,2-a:2'3'-c]phenazine, naphthalene-2-carboxylate, anthracene-9-carboxylate, pyrene-1-carboxylate and 1,10-phenanthroline have been studied for the first time by mass spectrometry. The probe electrospray ionization (PESI) is a technique based on electrospray ionization (ESI) that generates electrospray from the tip of a solid metal needle. In this work, mass spectra for organometallic complexes obtained by PESI were compared with those obtained by classical ESI and high flow rate electrospray ionization assisted by corona discharge (HF-ESI-CD), an ideal method to avoid decomposition of the complexes and to induce their oxidation to yield intact molecular cation radicals in gas state [M](+·) and to produce their reduction yielding the gas species [M](-·). It was found that both techniques showed in general the intact molecular ions of the organometallics studied and provided additional structure characteristic diagnostic fragments. As the rhenium complexes studied in the present work showed strong absorption in the UV-visible region, particularly at 355?nm, laser desorption ionization (LDI) mass spectrometry experiments could be conducted. Although intact molecular ions could be detected in a few cases, LDI mass spectra showed diagnostic fragments for characterization of the complexes structure. Furthermore, matrix-assisted laser desorption ionization (MALDI) mass spectra were obtained. Nor-harmane, a compound with basic character, was used as matrix, and the intact molecular ions were detected in two examples, in negative ion mode as the [M](-·) species. Results obtained with 2-[(2E)-3-(4-tert-buthylphenyl)-2-methylprop-2-enylidene] malononitrile (DCTB) as matrix are also described. LDI experiments provided more information about the rhenium complex structures than did the MALDI ones.     

On the distributions of ion/neutral molecule clusters in electrospray and laser spray—A cluster division model for the electrospray process

The clustering of a medium-sized, involatile, neutral molecule, octyl beta-D-glucopyranoside (OG), with Na(+), Ca(2+), and Yb(3+) (M(z+)) ions in electrospray (ESI) was investigated using laser spray (LSI). Extensive distributions of [(M(z+))(i) (OG)(a)](n+)-clusters, extending beyond 50 kDa, were observed. The distributions were highly stable and reproducible and changed only marginally when concentrations of electrolyte or neutral compound were varied by orders of magnitude. Compared with ESI, laser spray yielded superior intensities, particularly of the larger clusters. The cluster distributions demonstrated a range of remarkable features. In particular, the Yb(3+)/OG cluster distribution was unusual. For example, no clusters with 35-52 or with 110-116 OG molecules were observed. The distribution pattern revealed that the clusters were formed as a result of cluster dissociations, such as [(Yb(3+))(3)(OG) ( approximately 110)W](9+) --> [(Yb(3+))(2)(OG)( approximately 90)W](6+) + [(Yb(3+))(1)(OG) ( approximately 20)W](3+), where W represents the water content at the time of dissociation. Based on this study, a cluster division model for electrospray of aqueous solutions of strongly solvated ions is proposed: the Rayleigh droplet disintegration process, which is well-established for the initial stages of electrospray, maintains its general character as it proceeds through a final regime of multiply charged cluster dissociations to the singly and multiply charged ions in mass spectrometry. In the dissociation of multiply charged clusters, the size of each daughter cluster is roughly proportional to the square of the cluster charge. Observed cluster distributions are consistent with a mixture of symmetric and asymmetric cluster dissociations.     

Polymer segmental alignment in polarized pulsed laser-induced periodic surface structures

Received: 14 July 1997/Accepted: 15 July 1997