A comparison of collision cross section values obtained via travelling wave ion mobility-mass spectrometry and ultra high performance liquid chromatography-ion mobility-mass spectrometry : application to the characterisation of metabolites in rat urine

A comprehensive Collision Cross Section (CCS) library was obtained via Travelling Wave Ion Guide mobility measurements through direct infusion (DI). The library consists of CCS and Mass Spectral (MS) data in negative and positive ElectroSpray Ionisation (ESI) mode for 463 and 479 endogenous metabolites, respectively. For both ionisation modes combined, TWCCSN2 data were obtained for 542 non-redundant metabolites. These data were acquired on two different ion mobility enabled orthogonal acceleration QToF MS systems in two different laboratories, with the majority of the resulting TWCCSN2 values (from detected compounds) found to be within 1% of one another. Validation of these results against two independent, external TWCCSN2 data sources and predicted TWCCSN2 values indicated to be within 1-2% of these other values. The same metabolites were then analysed using a rapid reversed-phase ultra (high) performance liquid chromatographic (U(H)PLC) separation combined with IM and MS (IM-MS) thus providing retention time (tr), m/z and TWCCSN2 values (with the latter compared with the DI-IM-MS data). Analytes for which TWCCSN2 values were obtained by U(H)PLC-IM-MS showed good agreement with the results obtained from DI-IM-MS. The repeatability of the TWCCSN2 values obtained for these metabolites on the different ion mobility QToF systems, using either DI or LC, encouraged the further evaluation of the U(H)PLC-IM-MS approach via the analysis of samples of rat urine, from control and methotrexate-treated animals, in order to assess the potential of the approach for metabolite identification and profiling in metabolic phenotyping studies. Based on the database derived from the standards 63 metabolites were identified in rat urine, using positive ESI, based on the combination of tr, TWCCSN2 and MS data.</p

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Drawing a different picture with pencil lead as matrix-assisted laser desorption/ionization matrix for fullerene derivatives

Inspired by reports on the use of pencil lead as a matrix-assisted laser desorption/ionization matrix, paving the way towards matrix-free matrix-assisted laser desorption/ionization, the present investigation evaluates its usage with organic fullerene derivatives. Currently, this class of compounds is best analysed using the electron transfer matrix trans-2-[3-(4-tert-butylphenyl)-2-methyl-2-propenylidene] malononitrile (DCTB), which was employed as the standard here. The suitability of pencil lead was additionally compared to direct (i.e. no matrix) laser desorption/ionization-mass spectrometry. The use of (DCTB) was identified as the by far gentler method, producing spectra with abundant molecular ion signals and much reduced fragmentation. Analytically, pencil lead was found to be ineffective as a matrix, however, appears to be an extremely easy and inexpensive method for producing sodium and potassium adducts

C60H2: recovery and decline - an investigation by MALDI mass spectrometry

The smallest hydro-[60]fullerene, C60H2, has been studied by matrix-assisted laser desorption/ionisation (MALDI) mass spectrometry. The ionisation of C60H2 was accomplished for the first time free of unwanted dissociations in electron transfer reactions with cations derived from the DCTB matrix. The findings pave the way to the use of MALDI for the quantitation of lower hydrofullerenes or investigations into the release of hydrogen. Direct LDI and negative-ion MALDI are less suited for a meaningful analysis. However, negative-ion MALDI reveals that C60H2 degrades through oxidation. (C) 2010 Elsevier B.V. All rights reserved

Exploring the photoinduced electron transfer reactivity of aza[60]fullerene iminium cation

Photolysis of (C59N)2 solutions in the presence of neutral π-donors, such as arenes and electron-rich alkenes leads to a series of novel aza[60]fullerene monoadducts. The key step of the reaction involves a photoinduced electron transfer from the donor molecule to the iminium cation of aza[60]fullerene, followed by radical coupling of the resulting aza[60]fullerenyl radical with an intermediate stabilized radical derived from the substrate. This type of reactivity has been proven efficient with arenes having oxidation potential higher than about 1.5 V. Simple olefins, such as tri- and tetra-methylethylene, as well as cyclohexene, can also participate in this kind of photoinduced electron transfer-initiated reaction with C 59N+, affording the corresponding aza[60]fullerene derivatives. In the case of 2-methoxyprop-1-ene, 2,4-hexadiene, and β,β-dimethylstyrene, [2+2] cycloaddition reactions with the aza[60]fullerene carbon shell dominate, leading to a mixture of unidentified multiadducts. © 2010 Elsevier Ltd. All rights reserved

Ion formation pathways of crown ether–fullerene conjugates in the gas phase

The ion formation of crown ether–[60]fullerene conjugates of the type (crown − H)–C60–H with crown = 12cr4, 15cr5 and 18cr6 has been studied with matrix-assisted laser desorption/ionisation (MALDI) and electrospray ionisation mass spectrometry (ESI MS). In total five different ways of ion formation are presented, including metalation (MALDI, ESI), protonation and oxidation (both in MALDI) in the positive-ion mode and deprotonation (MALDI, ESI) and reduction (MALDI) in the negative-ion mode. In line with thermochemistry, the deprotonation and electron transfer processes involve the C60 moiety as the charge-carrying entity, while protonation and metalation occur at the crown ether. Particular emphasis has been placed on the study of metal cation attachment in MALDI varying the crown ether size in the conjugate and using different alkali metal chlorides in the target preparation. Dissociation reactions of the metalated conjugates are influenced by the interaction strength of the metal cation to the crown ether fullerene conjugate. The data confirm an increase in bond strength with smaller metal cations, supporting the notion of charge density-driven interactions

Dynamic HPLC study of C-70 chlorination reveals a surprisingly selective synthesis of C70Cl8

A dynamic HPLC study of C-70 chlorination led to the discovery, isolation, characterization, and development of the efficient preparatory procedures for two previously unknown soluble chlorofullerenes C70Cl8 and C70Cl6 and for insoluble [C70Cl8](n). A novel synthesis of 99% pure C70Cl10 with a nearly quantitative yield was also developed. The first stability study of C70Cl10,8,6 in solution showed that these compounds are very light-sensitive

Ultrahigh-performance liquid chromatography tandem mass spectrometry with electrospray ionization quantification of tryptophan metabolites and markers of gut health in serum and plasma-application to clinical and epidemiology cohorts

A targeted ultrahigh-performance liquid chromatography tandem mass spectrometry with electrospray ionization (UHPLC-ESI-MS/MS) method has been developed for the quantification of tryptophan and its downstream metabolites from the kynurenine and serotonin pathways. The assay coverage also includes markers of gut health and inflammation, including citrulline and neopterin. The method was designed in 96-well plate format for application in multiday, multiplate clinical and epidemiology population studies. A chromatographic cycle time of 7 min enables the analysis of two 96-well plates in 24 h. To protect chromatographic column lifespan, samples underwent a two-step extraction, using solvent protein precipitation followed by delipidation via solid-phase extraction (SPE). Analytical validation reported accuracy of each analyte &lt;20% for the lowest limit of quantification and &lt;15% for all other quality control (QC) levels. The analytical precision for each analyte was 2.1-12.9%. To test the applicability of the method to multiplate and multiday preparations, a serum pool underwent periodic repeat analysis during a run consisting of 18 plates. The % CV (coefficient of variation) values obtained for each analyte were &lt;15%. Additional biological testing applied the assay to samples collected from healthy control participants and two groups diagnosed with inflammatory bowel disease (IBD) (one group treated with the anti-inflammatory 5-aminosalicylic acid (5-ASA) and one group untreated), with results showing significant differences in the concentrations of picolinic acid, kynurenine, and xanthurenic acid. The short analysis time and 96-well plate format of the assay makes it suitable for high-throughput targeted UHPLC-ESI-MS/MS metabolomic analysis in large-scale clinical and epidemiological population studies.</p