Background: The majority of ovarian cancer biomarker discovery efforts focus on the identification of proteins that can improve the predictive power of presently available diagnostic tests. We here show that metabolomics, the study of metabolic changes in biological systems, can also provide characteristic small molecule fingerprints related to this disease.

We report a route to synthesize a wide range of organophosphates of biological significance in a deep eutectic solvent (2:1 urea and choline chloride), utilizing various orthophosphate sources. Heating an organic alcohol in the solvent along with a soluble phosphorus source yields phosphorus esters of choline as well as that of the added organic in yields between 15 to 99 %. In addition, phosphite analogs of biological phosphates and peptides were also formed by the simple mixing of reagents and heating at 60-70 °C in the deep eutectic solvent. The presented dehydration reactions are relevant to prebiotic and green chemistry in alternative solvents.

Metabolomic fingerprinting of bodily fluids can reveal the underlying causes of metabolic disorders associated with many diseases, and has thus been recognized as a potential tool for disease diagnosis and prognosis following therapy. Here we report a rapid approach in which direct analysis in real time (DART) coupled with time-of-flight (TOF) mass spectrometry (MS) and hybrid quadrupole TOF (Q-TOF) MS is used as a means for metabolomic fingerprinting of human serum. In this approach, serum samples are first treated to precipitate proteins, and the volatility of the remaining metabolites increased by derivatization, followed by DART MS analysis. Maximum DART MS performance was obtained by optimizing instrumental parameters such as ionizing gas temperature and flow rate for the analysis of identical aliquots of a healthy human serum samples. These variables were observed to have a significant effect on the overall mass range of the metabolites detected as well as the signal-to-noise ratios in DART mass spectra. Each DART run requires only 1.2 min, during which more than 1500 different spectral features are observed in a time-dependent fashion. A repeatability of 4.1% to 4.5% was obtained for the total ion signal using a manual sampling arm. With the appealing features of high-throughput, lack of memory effects, and simplicity, DART MS has shown potential to become an invaluable tool for metabolomic fingerprinting. (J Am Soc Mass Spectrom 2010, 21, 68 -75) © 2010 American Society for Mass Spectrometry M etabolomic fingerprinting, an unbiased, global screening approach to classify samples based on metabolite patterns or "fingerprints", has been performed in a wide variety of biological sample types such as urine, plasma, serum, and tissues [1]. Nuclear magnetic resonance (NMR) and mass spectrometry are two widely used analytical platforms applied to metabolomic fingerprinting. NMR has the advantage of requiring little sample preparation, and of producing datasets that are more easily mined [2-4], but cost and sensitivity are two of its major limitations. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) are two additional techniques commonly used in metabolomic workflows [1,[5][6][7][8][9]. Despite being extremely comprehensive, GC-MS and LC-MS suffer from low analysis throughput and memory effects of the chromatographic supports, particularly when investigating metabolites in biological matrices such as serum. To overcome the above described limitations, enabling technologies for the effective analysis of metabolomes are still rapidly evolving.Direct analysis in real time (DART) is a plasma-based ion generation technique that operates under ambient conditions. It belongs to a wider family of ambient plasma ionization techniques that includes direct atmospheric pressure photo-ionization (DAPPI) [10], direct analysis in real time (DART) [11], flowing atmospheric pressure afterglow (FAPA) [12], plasma-assisted desorption ionization (PADI) [13], desorption atmospheric pre...

Following his seminal work in 1953, Stanley Miller conducted an experiment in 1958 to study the polymerization of amino acids under simulated early Earth conditions. In the experiment, Miller sparked a gas mixture of CH4, NH3, and H2O, while intermittently adding the plausible prebiotic condensing reagent cyanamide. For unknown reasons, an analysis of the samples was not reported. We analyzed the archived samples for amino acids, dipeptides, and diketopiperazines by liquid chromatography, ion mobility spectrometry, and mass spectrometry. A dozen amino acids, 10 glycine-containing dipeptides, and 3 glycine-containing diketopiperazines were detected. Miller's experiment was repeated and similar polymerization products were observed. Aqueous heating experiments indicate that Strecker synthesis intermediates play a key role in facilitating polymerization. These results highlight the potential importance of condensing reagents in generating diversity within the prebiotic chemical inventory.

Dental composites undergo material property changes during exposure to the oral environment and may release compounds of potential toxicity, such as bisphenol A. Degradation of dental composites was studied in a simplified overlayer model in which bisphenol A diglycidyl methacrylate (BisGMA) was covalently bound to a porous silicon oxide surface. It was hypothesized that the chemical structure of this overlayer would allow release of bisphenol A, BisGMA, and the decomposition products thereof, upon exposure to water for an extended period. Liquid chromatography mass spectrometry found leaching of intact BisGMA and several degradation products that contained the bisphenol A moiety from the overlayer into distilled water after 2 wks of aging. The absence of bisphenol A release from the overlayer reduces concerns regarding its potential health risk in dental composites. Nevertheless, health concerns might arise with respect to BisGMA and the leached degradation products, since they all contain the bisphenol A moiety. Abbreviations: BisGMA, bisphenol A diglycidyl methacrylate; HPLC, high-performance liquid chromatography; LCMS, liquid chromatography mass spectrometry; MA, methacrylic acid; MPS, 3-(trimethoxysilyl) propyl methacrylate; m/z, mass-to-charge ratio; and TIC, total ion chromatogram.