A variety of gram-positive and gram-negative intact bacterial cells have been analysed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and shown to provide fingerprint mass spectra with discrete peaks being observed over the mass range from 3 to 40 kDa. The spectra show both more peaks and peaks at a higher mass/charge ratio than have hitherto been reported for these micro-organisms and would appear to provide a profile of cellular proteinaceous material. The spectra are shown to be reproducible over variable time periods of up to three months and factors affecting reproducibility are discussed. The procedure, which requires minimal sample preparation, yields results in 30-40 minutes and allows visual identification of species-and strain-specific biomarkers for the characterization of the organisms. The importance of accurately defining sample preparation methodologies is central to the ability of the technique to generate reliable and reproducible data.

Glioblastoma (GBM) is an aggressive primary human brain tumour that has resisted effective therapy for decades. Although glucose and glutamine are the major fuels that drive GBM growth and invasion, few studies have targeted these fuels for therapeutic management. The glutamine antagonist, 6-diazo-5-oxo-L-norleucine (DON), was administered together with a calorically restricted ketogenic diet (KD-R) to treat late-stage orthotopic growth in two syngeneic GBM mouse models: VM-M3 and CT-2A. DON targets glutaminolysis, while the KD-R reduces glucose and, simultaneously, elevates neuroprotective and non-fermentable ketone bodies. The diet/drug therapeutic strategy killed tumour cells while reversing disease symptoms, and improving overall mouse survival. The therapeutic strategy also reduces edema, hemorrhage, and inflammation. Moreover, the KD-R diet facilitated DON delivery to the brain and allowed a lower dosage to achieve therapeutic effect. The findings support the importance of glucose and glutamine in driving GBM growth and provide a therapeutic strategy for non-toxic metabolic management.

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Variations in molecular mass distributions observed by matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry as a function of changes in the ion accelerating voltage and composition of the matrix have been investigated, using the pyridine-insoluble fraction of a coal tar pitch. With increasing ion extraction voltages (10, 20 and 30 kV) and in the absence of added matrix, spectra clearly showed increases in intensity, particularly at higher masses. The use of higher ion extraction voltages may be considered as providing a more complete inventory of ionized species, apparently significantly enhancing the kinetic energy imparted to larger molecular weight materials. Magnitudes of molecular masses at maximum ion intensity observed using a set of different matrices may be ordered as follows: m/z 1500 [dimethoxy-4-hydroxycinnamic (sinapinic) acid], m/z 1400 (2,5-dihydroxybenzoic acid), m/z 900 [2-(4-hydroxyphenylazo)-benzoic acid], m/z 900 (α-cyano-3-hydroxycinnamic acid), m/z 300 (9-anthracenecarboxylic acid) and m/z 300 (no matrix and a sample loading comparable with the with-matrix experiments). Maximum ion intensities, in the absence of matrix, were found at values which varied from about 300 m/z up to about m/z 1500 as sample loading varied from very low (i.e. suitable for with-matrix operation) up to a visibly black spot. In the absence of a quantitatively based criterion for distinguishing between signal and instrument noise at high mass, accurate high mass limits were not available. However, in each case, ion signals could clearly be observed at values greater than m/z 100 000. The present MALDI spectra do not necessarily show the highest molecular mass materials present in the sample. In view of the observed changes in the spectra with ion extraction voltage and matrix composition, it seems conceivable that higher voltages and/or specific matrices, other than those used in the study, may lead to the detection of larger molecules. © 1997 by John Wiley & Sons, Ltd. Received 23 December 1996; Revised 3 February 1997; Accepted 25 February 1997 Rapid. Commun. Mass Spectrom. 11, 638-645 (1997 Characterization by laser desorption mass spectrometry has considerably extended the range of molecular masses identified in coal-derived liquids. The work was initially undertaken in an attempt to provide independent confirmation for the identification of molecular masses (MMs) up to 4-6000 Da found by size-exclusion chromatography (SEC).1-5 During this preliminary stage of the study, MMs up to the limit of a LIMA (laser ionization mass analysis) instrument (m/z 12 000) were detected in liquefaction extracts and in a coal tar pitch. [6][7][8][9] In these experiments, the reflectron flight path caused loss of detection at high mass but the instrument could not be operated in linear mode. Experiments were conducted at an ion extraction voltage of 20 kV and with a defocused primary beam to prevent the breaking up of sample molecules due to the power of the laser. However, lacking a spectrum additio...

Rapid and versatile direct analysis in real time mass spectrometry (DART-MS) methods were developed for detection and characterization of synthetic cathinone designer drugs, also known as "bath salts". The speed and efficiency associated with DART-MS testing of such highly unpredictable samples demonstrate the technique as an attractive alternative to conventional GC-MS and LC-MS methods. A series of isobaric and closely related synthetic cathinones, alone and in mixtures, were differentiated using high mass accuracy and in-source collision induced dissociation (CID). Crime laboratories have observed a dramatic rise in the use of these substances, which has caused sample testing backlogs, particularly since the myriad of structurally related compounds are challenging to efficiently differentiate. This challenge is compounded by the perpetual emergence of new structural variants as soon as older generation derivatives become scheduled. Because of the numerous chemical substances that fall into these categories, along with the varying composition and complexity of mixtures of these drugs, DART-MS CID has the potential to dramatically streamline sample analysis, minimize the number of sample preparation steps, and enable rapid characterization of emerging structural analogs.