A 0535+26: Back in business

In May/June 2005, after 10 years of inactivity, the Be/X-ray binary system A 0535+26 underwent a major X-ray outburst. In this paper data are presented from 10 years of optical, IR and X-ray monitoring showing the behaviour of the system during the quiescent epoch and the lead up to the new outburst. The results show the system going through a period when the Be star in the system had a minimal circumstellar disk and then a dramatic disk recovery leading, presumably, to the latest flare up of X-ray emission. The data are interpreted in terms of the state of the disk and its interaction with the neutron star companion.Comment: Accepted for publication in MNRA

The key role of mass spectrometry in comprehensive research on new psychoactive substances

New psychoactive substances (NPS) are a wide group of compounds that try to mimic the effects produced by the ‘classical’ illicit drugs, including cannabis (synthetic cannabinoids), cocaine and amphetamines (synthetic cathinones) or heroin (synthetic opioids), and which health effects are still unknown for most of them. Nowadays, more than 700 compounds are being monitored by official organisms, some of which have been recently identified in seizures and/or intoxication cases. Toxicological analysis plays a pivotal role in NPS research. A comprehensive investigation on NPS, from the first identification of a novel substance until its detection in drug users to help in diagnostics and medical treatment, requires the use of a wide variety of instruments and analytical strategies. This paper illustrates the key role of mass spectrometry (MS) along a comprehensive investigation on NPS. The synthetic cannabinoid XLR‐11 and the synthetic cathinone 5‐PPDi have been chosen as representative substances of the most consumed NPS families. Moreover, both compounds have been investigated at our laboratory in different stages of the three‐step strategy considered in this article. The initial identification and characterisation of the compound in consumption products, the first reported metabolic pathway and the development of analytical methodologies for its determination (and/or their metabolites) in different toxicological samples are described. The analytical strategies and MS instruments are briefly discussed to show the reader the possibilities that MS instrumentation offer to analytical scientists. This publication aims to be a starting point for those interested on the NPS research field from an analytical chemistry point of view

Photometric observations of the radio bright B[e]/X-ray binary CI Cam

We present multiwavelength (optical, IR, radio) observations of CI Cam, the optical counterpart to the transient X-ray source XTE J0421+560. Pre-outburst quiescent observations reveal the presence of a dusty envelope around the system. Pronounced short term variability is observed at all wavebands from U-K, but no indication of prior flaring of a similar magnitude to the 1998 April outburst is found in these data. Data obtained during the 1998 April X-ray flare reveal pronounced optical-radio flaring. The optical flux was observed to quickly return to quiescent levels, while the radio flare was of much longer duration. The optical component is likely to result from a combination of free-free/free-bound emission, emission line and thermal dust emission, caused by re-radiation of the X-ray flux, while the behaviour of the multiwavelength radio data is consistent with emission from expanding ejecta emitting via the synchrotron mechanism. Post-outburst (1998 August-1999 March) U-M broadband photometric observations reveal that while the optical (UBV) flux remains at pre-outburst quiescent levels, near IR (JHKLM) fluxes exceed the pre-outburst fluxes by ~0.5 magnitudes. Modelling the pre- and post-outburst spectral energy distribution of CI Cam reveals that the structure and/or composition of the dusty component of the circumstellar envelope appears to have changed. Due to a lack of information on the precise chemical composition of the dust within the system several explanations for this behaviour are possible, such as the production of new dust at the inner edge of the envelope, or modification of the composition of the dust due to X-ray irradiation

Metabolic profiling of four synthetic stimulants, including the novel indanyl-cathinone 5-PPDi, after human hepatocyte incubation

Synthetic cathinones are new psychoactive substances that represent a health risk worldwide. For most of the 130 reported compounds, information about toxicology and/or metabolism is not available, which hampers their detection (and subsequent medical treatment) in intoxication cases. The principles of forensic analytical chemistry and the use of powerful analytical techniques are indispensable for stablishing the most appropriate biomarkers for these substances. Human metabolic fate of synthetic cathinones can be assessed by the analysis of urine and blood obtained from authentic consumers; however, this type of samples is limited and difficult to access. In this work, the metabolic behaviour of three synthetic cathinones (4-CEC, 4-CPrC and 5-PPDi) and one amphetamine (3-FEA) has been evaluated by incubation with pooled human hepatocytes and metabolite identification has been performed by high-resolution mass spectrometry. This in vitro approach has previously shown its feasibility for obtaining excretory human metabolites. 4-CEC and 3-FEA were not metabolised, and for 4-CPrC only two minor metabolites were obtained. On the contrary, for the recently reported 5-PPDi, twelve phase I metabolites were elucidated. Up to our knowledge, this is the first metabolic study of an indanyl-cathinone. Data reported in this paper will allow the detection of these synthetic stimulants in intoxication cases, and will facilitate future research on the metabolic behaviour of other indanyl-based cathinones

Fast methodology for the reliable determination of nonylphenol in water samples by minimal labeling isotope dilution mass spectrometry

In this work we have developed and validated an accurate and fast methodology for the determination of 4-nonylphenol (technical mixture) in complex matrix water samples by UHPLC–ESI-MS/MS. The procedure is based on isotope dilution mass spectrometry (IDMS) in combination with isotope pattern deconvolution (IPD), which provides the concentration of the analyte directly from the spiked sample without requiring any methodological calibration graph. To avoid any possible isotopic effect during the analytical procedure the in-house synthesized 13C1-4-(3,6-dimethyl-3-heptyl)phenol was used as labeled compound. This proposed surrogate was able to compensate the matrix effect even from wastewater samples. A SPE pre-concentration step together with exhaustive efforts to avoid contamination were included to reach the signal-to-noise ratio necessary to detect the endogenous concentrations present in environmental samples. Calculations were performed acquiring only three transitions, achieving limits of detection lower than 100 ng/g for all water matrix assayed. Recoveries within 83–108% and coefficients of variation ranging from 1.5% to 9% were obtained. On the contrary a considerable overestimation was obtained with the most usual classical calibration procedure using 4-n-nonylphenol as internal standard, demonstrating the suitability of the minimal labeling approach

Proposal of 5-methoxy-N-methyl-N-isopropyltryptamine consumption biomarkers through identification of in vivo metabolites from mice

New psychoactive substances (NPS) are a new breed of synthetically produced substances designed to mimic the effects of traditional illegal drugs. Synthetic cannabinoids and synthetic cathinones are the two most common groups, which try to mimic the effects of the natural compounds 9Δ-tetrahydrocannabinol and cathinone, respectively. Similarly, synthetic tryptamines are designer compounds which are based on the compounds psilocin, N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine found in some mushrooms. One of the most important tryptamine compounds found in seizures is 5-methoxy-N,N-diisopropyltryptamine, which has been placed as controlled substance in USA and some European countries. The control of this compound has promoted the rising of another tryptamine, the 5-methoxy-N-methyl-N-isopropyltryptamine, which at the time of writing this article has not been banned yet. So, it is undeniable that this new substance should be monitored. 5-methoxy-N-methyl-N-isopropyltryptamine has been reported by the Spanish Early Warning System and detected in our laboratory in two pill samples purchased in a local smart shop. This has promoted the need of stablishing consumption markers for this compound in consumers’ urine. In the present work, the metabolism and pharmacokinetic of 5-methoxy-N-methyl-N-isopropyltryptamine has been studied by an in vivo approach, using adult male mice of the inbred strain C57BLJ/6. The use of ultra-high performance liquid chromatography coupled to high resolution mass spectrometry allowed the identification of four metabolites. After the pharmacokinetic study in serum and urine, the O-demethylated metabolite and the non-metabolised parent compound are proposed as consumption markers in hydrolysed urine. Data reported in this work will help hospitals and forensic laboratories to monitor the consumption and potential intoxication cases related to this tryptamine

Comparison of approaches to deal with matrix effects in LC-MS/MS based determinations of mycotoxins in food and feed

This study deals with one of the major concerns in mycotoxin determinations: the matrix effect related to LC-MS/ MS systems with electrospray ionization sources. To this end, in a first approach, the matrix effect has been evaluated in two ways: monitoring the signal of a compound (added to the mobile phase) during the entire chromatographicrun, and by classical post-extraction addition. The study was focused on nine selected mycotoxins: aflatoxin B1, fumonisins B1, B2 and B3, ochratoxin A, deoxynivalenol, T-2 and HT-2 toxins and zearalenone in various sample extracts giving moderate to strong matrix effects (maize, compound feed, straw, spices). Although the permanent monitoring of a compound provided a qualitative way of evaluating the matrix effects at each retention time, we concluded that it was not adequate as a quantitative approach to correct for the matrix effect. Matrix effects measured by post-extraction addition showed that the strongest ion suppression occurred for the spices (up to -89%). Five different calibration approaches to compensate for matrix effects were compared: multi-level external calibration using isotopically labelled internal standards, multi-level and single level standard addition, and two ways of singlepoint internal calibration: one point isotopic internal calibration and isotope pattern deconvolution. In general, recoveries and precision meeting the European Union requirements could be achieved with all approaches, with the exception of the single level standard addition at levels too close to the concentration in the sample. When an isotopically labelled internal standard is not available, single-level standard addition is the most efficient option.The Dutch Ministry of Economic Affairs is acknowledged for financially supporting this work. The authors acknowledge the financial support from Generalitat Valenciana (Research group of excellence Prometeo 2009/054 and Collaborative Research on Environment and Food Safety ISIC/2012/016). N. Fabregat-Cabello also acknowledges the Generalitat Valenciana for her Ph.D. research grant under the Program VALi+D

Snail blocks the cell cycle and confers resistance to cell death

The Snail zinc-finger transcription factors trigger epithelial-mesenchymal transitions (EMTs), endowing epithelial cells with migratory and invasive properties during both embryonic development and tumor progression. During EMT, Snail provokes the loss of epithelial markers, as well as changes in cell shape and the expression of mesenchymal markers. Here, we show that in addition to inducing dramatic phenotypic alterations, Snail attenuates the cell cycle and confers resistance to cell death induced by the withdrawal of survival factors and by pro-apoptotic signals. Hence, Snail favors changes in cell shape versus cell division, indicating that with respect to oncogenesis, although a deregulation/increase in proliferation is crucial for tumor formation and growth, this may not be so for tumor malignization. Finally, the resistance to cell death conferred by Snail provides a selective advantage to embryonic cells to migrate and colonize distant territories, and to malignant cells to separate from the primary tumor, invade, and form metastasis

Direct and Fast Screening of New Psychoactive Substances Using Medical Swabs and Atmospheric Solids Analysis Probe Triple Quadrupole with Data-Dependent Acquisition

New psychoactive substances (NPS) have become a serious public health problem, as they are continuously changing their structures and modifying their potency and effects on humans, and therefore, novel compounds are unceasingly appearing. One of the major challenges in forensic analysis, particularly related to the problem of NPS, is the development of fast screening methodologies that allow the detection of a wide variety of compounds in a single analysis. In this study, a novel application of the atmospheric solids analysis probe (ASAP) using medical swabs has been developed. The swab–ASAP was coupled to a triple quadrupole mass analyzer working under a data-dependent acquisition mode in order to perform a suspect screening of NPS in different types of samples as well as on surfaces. The compounds were automatically identified based on the observed fragmentation spectra using an in-house built MS/MS spectra library. The developed methodology was applied for the identification of psychoactive substances in research chemicals and herbal blends. The sensitivity of the method, as well as its applicability for surface analysis, was also assessed by identifying down to 1 μg of compound impregnated onto a laboratory table. Another remarkable application was the identification of cathinones and synthetic cannabinoids on the fingers of potential consumers. Interestingly, our data showed that NPS could be identified on the fingers after being in contact with the product and even after cleaning their hands by shaking off with a cloth. The methodology proposed in this paper can be applied for routine analyses of NPS in different matrix samples without the need to establish a list of target compounds prior to analysis

Hß photometry for uvby standard stars

From 1984 to 1986, we made several observational campaigns at Calar Alto and La Palma Observator­ies using the uvby and ß photometric systems to monitor a selected sample of late-type variable stars. In this paper we present the ß values for 38 uvby standard stars to contribute to the uvby-ß calibration works on late-type stars. In the final discussion, the ß computed values are plotted against the Ström­gren b - y, m_1, and c_1 indices