Multi-class determination of around 50 pharmaceuticals, including 26 antibiotics, in environmental and wastewater samples by ultra-high performance liquid chromatography-tandem mass spectrometry

A multi-class method for the simultaneous quantification and confirmation of 47 pharmaceuticals in environmental and wastewater samples has been developed. The target list of analytes included analgesic and anti-inflammatories, cholesterol lowering statin drugs and lipid regulators, antidepressants, anti-ulcer agents, psychiatric drugs, ansiolitics, cardiovasculars and a high number (26) of antibiotics from different chemical groups. A common pre-concentration step based on solid-phase extraction with Oasis HLB cartridges was applied, followed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) measurement. All compounds were satisfactorily determined in just one single injection, with a chromatographic run time of only 10 min. The process efficiency (combination of the matrix effect and the extraction process recovery) for the 47 selected compounds was evaluated in nine effluent wastewater (EWW) samples, and the use of different isotope-labelled internal standards (ILIS) was investigated to correct unsatisfactory values. Up to 12 ILIS were evaluated in EWW and surface water (SW). As expected, the ILIS provided satisfactory correction for their own analytes. However, the use of these ILIS for the rest of pharmaceuticals was problematic in some cases. Despite this fact, the correction with analogues ILIS was found useful for most of analytes in EWW, while was not strictly required in the SW tested. The method was successfully validated in SW and EWW at low concentration levels, as expected for pharmaceuticals in these matrices (0.025, 0.1 and 0.5 μg/L in SW; 0.1 and 0.5 μg/L in EWW). With only a few exceptions, the instrumental limits of detection varied between 0.1 and 8 pg. The limits of quantification were estimated from sample chromatograms at the lowest spiked levels tested and normally were below 20 ng/L for SW and below 50 ng/L for EWW. The developed method was applied to the analysis of around forty water samples (river waters and effluent wastewaters) from the Spanish Mediterranean region. Almost all the pharmaceuticals selected in this work were detected, mainly in effluent wastewater. In both matrices, analgesics and anti-inflammatories, lipid regulators and quinolone antibiotics were the most detected groups.     

Highly Selective Barbier‐Type Propargylations and Allenylations Catalyzed by Titanocene(III)

The alkyne functional group is found in many bioactive natural products and is the key to many important chemical transformations developed over recent years. Moreover, allenes have recently gained relevance as versatile reagents in organic synthesis. Mild, catalytic methods to enable the selective introduction of either alkyne or allene motifs into organic molecules are very valuable but, as yet, quite scarce. We describe an extremely mild and selective method for either the propargylation or allenylation of carbonyl compounds catalyzed by the abundant, safe, and inexpensive metal titanium. These reactions can selectively provide homopropargylic alcohols from aldehydes and ketones or α‐hydroxy‐allenes from aldehydes. The mechanisms involved were also investigated.     

Facile two-electron reduction of a closo-rhodathiadecaborane

Closo-to-arachno redox flexibility in metallaheteroboranes may be viewed as a metal-to-ligand cooperative action with application in catalysis. The treatment of [PSH][arachno-4-SB(8)H(11)] with [RhCl(PPh(3))(3)] affords, after chromatography, three new 10-vertex rhodathiaboranes, [2,2,2-(H)(PPh(3))(2)-closo-2,1-RhSB(8)H(8)] (3), [6,6,9-(PPh(3))(3)-arachno-6,5-RhSB(8)H(9)] (4) and [2,2,2-(Cl)(H)(PPh(3))-6-(PPh(3))-closo-2,1-RhSB(8)H(7)] (5). 3 reacts quantitatively with PPh(3) to form 4, which, in turn, reacts with chlorinated solvents to give the chloro-ligated cluster 5. Kinetic studies demonstrate that the reaction of 3 with PPh(3) obeys a second-order rate law, with an associative mechanism. The Lewis acidity of 3 is quite remarkable, and, given its closo-to-arachno structural and electronic response, this cluster is expected to exhibit a rich chemistry.     

Multi-residue determination of pesticides in tropical fruits using liquid chromatography/tandem mass spectrometry

Monitoring pesticide residues in tropical fruits is of great interest for many countries, e.g., from South America, that base an important part of their economy on the exportation of these products. In this work, a LC-MS/MS multi-residue method using a triple quadrupole analyzer has been developed for around 30 pesticides in seven Colombian tropical fruits of high commercial value for domestic and international markets (uchuva, tamarillo, granadilla, gulupa, maracuya, papaya, and pithaya). After sample extraction with acetonitrile, an aliquot of the extract was diluted with water and directly injected into the HPLC-MS/MS system (electrospray interface) without any cleanup step. The formation of sodium adducts—of poor fragmentation—was minimized using 0.1% formic acid in the mobile phase, which favored the formation of the protonated molecule. However, the addition of ammonium acetate made the formation of the ammonium adducts in some particular cases possible, avoiding the presence of the sodium adducts. The highest sensitivity was observed in positive electrospray ionization for the wide majority of pesticides, with a few exceptions for acidic compounds that gave better response in the negative mode (e.g., 2,4-D, fluazinan). Thus, simultaneous acquisition on the positive/negative mode was applied. Two MS/MS transitions were acquired for each compound to ensure a reliable quantification and identification of the compounds detected in samples, although for malathion a third transition was acquired due to the presence of interfering isobaric compounds in the sample extracts. A detailed study of matrix effects was made by a comparison of standards in solvent and in matrix. Both ionization suppression and ionization enhancement were observed depending on the analyte/matrix combination tested. Correction of matrix effects was made by the application of calibration in matrix. Three matrices were selected (uchuva, maracuya, gulupa) to perform matrix calibration in the analysis of all seven fruit varieties studied. The method was validated by recovery experiments in samples spiked at two levels (0.05 and 0.5 mg/kg). The data were satisfactory for the wide majority of analyte/matrix combinations, with most recoveries between 70% and 110% and the RSD below 15%. Several samples collected from the market were finally analyzed. Positive findings were confirmed by evaluating the experimental Q/q ratios and retention times, and comparing them with those of reference standards.     

Importance of MS selectivity and chromatographic separation in LC-MS/MS-based methods when investigating pharmaceutical metabolites in water. Dipyrone as a case of study

Pharmaceuticals are emerging contaminants of increasing concern because of their presence in the aquatic environment and potential to reach drinking-water sources. After human and/or veterinary consumption, pharmaceuticals can be excreted in unchanged form, as the parent compound, and/or as free or conjugated metabolites. Determination of most pharmaceuticals and metabolites in the environment is commonly made by liquid chromatography (LC) coupled to mass spectrometry (MS). LC coupled to tandem MS is the technique of choice nowadays in this field. The acquisition of two selected reaction monitoring (SRM) transitions together with the retention time is the most widely accepted criterion for a safe quantification and confirmation assay. However, scarce attention is normally paid to the selectivity of the selected transitions as well as to the chromatographic separation. In this work, the importance of full spectrum acquisition high-resolution MS data using a hybrid quadrupole time-of-flight analyser and/or a suitable chromatographic separation (to reduce the possibility of co-eluting interferences) is highlighted when investigating pharmaceutical metabolites that share common fragment ions. For this purpose, the analytical challenge associated to the determination of metabolites of the widely used analgesic dipyrone (also known as metamizol) in urban wastewater is discussed. Examples are given on the possibilities of reporting false positives of dypirone metabolites by LC-MS/MS under SRM mode due to a wrong assignment of identity of the compounds detected. Copyright ? 2012 John Wiley & Sons, Ltd.     

Statistical Physics Approach to Thermophoresis of Colloids

Brownian colloidal particles dispersed in a fluid with a temperature gradient experience a driving force which produces a large biased steady density profile. This phenomenon, named thermophoresis, is quantified by the Soret coefficient \(S_T\). This problem is studied here within the Fokker–Planck formalism. Using the experimental observation of \(S_T\) it is possible to extract relevant analytical information about a temperature dependent nonequilibrium effective potential which can produce the thermophoresis force. It will be presented here a statistical physics derivation of this effective potential in terms of some physical parameters. Experimental data are analyzed within this theoretical scenario.     

Prospects of warm dense matter research at HiRadMat facility at CERN using 440 MeV SPS proton beam

In this paper we present numerical simulations of heating of a solid copper cylinder by the 440 GeV proton beam delivered by the Super Proton Synchrotron (SPS) at CERN. The beam is made of 288 proton bunches while each bunch comprises of 1.15·10¹¹ so that the total number of protons in the beam is about 1.3·10¹³. The bunch length is 0.5 ns while two neighboring bunches are separated by 25 ns so that the beam duration is 7.2 μs. Particle intensity distribution in the transverse direction is a Gaussian and the beam can be focused to a spot size with σ = 0.1 mm–1.0 mm. In this paper we present results using two values of σ, namely 0.2 mm and 0.5 mm, respectively. The target length is 1.5 m with a radius = 5 cm and is facially irradiated by the beam. The energy deposition code FLUKA and the two-dimensional hydrodynamic code BIG2 are employed using a suitable iteration time to simulate the hydrodynamic and the thermodynamic response of the target. The primary purpose of this work was to design fixed target experiments for the machine protection studies at the HiRadMat (High Radiation Materials) facility at CERN. However this work has shown that large samples of High Energy Density (HED) matter will be generated in such experiments which suggests an additional application of this facility. In the present paper we emphasize the possibility of doing HED physics experiments at the HiRadMat in the future.     

Fourier-Mukai transforms for Gorenstein schemes

We extend to singular schemes with Gorenstein singularities or fibered in schemes of that kind Bondal and Orlov's criterion for an integral functor to be fully faithful. We also prove that the original condition of characteristic zero cannot be removed by providing a counterexample in positive characteristic. We contemplate a criterion for equivalence as well. In addition, we prove that for locally projective Gorenstein morphisms, a relative integral functor is fully faithful if and only if its restriction to each fibre is also fully faithful. These results imply the invertibility of the usual relative Fourier-Mukai transform for an elliptic fibration as a direct corollary.     

Physical properties of voltage gated pores

Experiments on single ionic channels have contributed to a large extent to our current view on the function of cell membrane. In these experiments the main observables are the physical quantities: ionic concentration, membrane electrostatic potential and ionic fluxes, all of them presenting large fluctuations. The classical theory of Goldman–Hodking–Katz assumes that an open channel can be well described by a physical pore where ions follow statistical physics. Nevertheless real molecular channels are active pores with open and close dynamical states. By skipping the molecular complexity of real channels, here we present the internal structure and calibration of two active pore models. These models present a minimum set of degrees of freedom, specifically ion positions and gate states, which follow Langevin equations constructed from a unique potential energy functional and by using standard rules of statistical physics. Numerical simulations of both models are implemented and the results show that they have dynamical properties very close to those observed in experiments of Na and K molecular channels. In particular a significant effect of the external ion concentration on gating dynamics is predicted, which is consistent with previous experimental observations. This approach can be extended to other channel types with more specific phenomenology.