Determination of cocaine and metabolites in hair by column-switching LC-MS-MS analysis

A method for rapid, selective, and robust determination of cocaine (CO) and metabolites in 5-mg hair samples was developed and fully validated using a column-switching liquid chromatography–tandem mass spectrometry system (LC-MS-MS). Hair samples were decontaminated, segmented, incubated overnight in diluted HCl, and centrifuged, and the diluted (1:10 with distilled water) extracts were analyzed in positive ionization mode monitoring two reactions per analyte. Quantifier transitions were: m/z 304.2→182.2 for CO, m/z 290.1→168.1 for benzoylecgonine (BE), and m/z 318.2→196.2 for cocaethylene (CE). The lower limit of quantification (LLOQ) was set at 0.05 ng/mg for CO and CE, and 0.012 ng/mg for BE. Imprecision and inaccuracy at LLOQ were lower than 20 % for all analytes. Linearity ranged between 0.05 and 50.0 ng/mg for CO and CE and 0.012 and 12.50 ng/mg for BE. Selectivity, matrix effect, process efficiency, recovery, carryover, cross talk, and autosampler stability were also evaluated during validation. Eighteen real hair samples and five samples from a commercial proficiency testing program were comparatively examined with the proposed multidimensional chromatography coupled with tandem mass spectrometry procedure and our reference gas chromatography coupled to mass spectrometry (GC-MS) method. Compared with our reference GC-MS method, column-switching technique and the high sensitivity of the tandem mass spectrometry detection system allowed to significantly reduce sample amount (×10) with increased sensitivity (×2) and sample throughput (×4), to simplify sample preparation, and to avoid that interfering compounds and ions impaired the ionization and detection of the analytes and deteriorate the performance of the ion source.     

Evaluation of flavonols and derivatives as human cathepsin B inhibitor

Cathepsin B (catB) is a cysteine protease involved in tumour progression and represents a potential therapeutic target in cancer. Among the 15 evaluated extracts from cerrado biome, Myrcia lingua Berg. (Myrtaceae) extract demonstrated to be a source of compounds with potential to inhibit catB. Using bioactivity-guided fractionation, we have found flavonols as inhibitors and also some other derivatives were obtained. From the evaluated compounds, myricetin (5) and quercetin (6) showed the most promising results with IC₅₀ of 4.9 and 8.2 μM, respectively, and mode of inhibition as uncompetitive on catB. The results demonstrated polyhydroxylated flavonols as promising inhibitors of catB.     

Multifractality through Non-Markovian Stochastic Processes in the Scale Relativity Theory. Acute Arterial Occlusions as Scale Transitions

By assimilating biological systems, both structural and functional, into multifractal objects, their behavior can be described in the framework of the scale relativity theory, in any of its forms (standard form in Nottale’s sense and/or the form of the multifractal theory of motion). By operating in the context of the multifractal theory of motion, based on multifractalization through non-Markovian stochastic processes, the main results of Nottale’s theory can be generalized (specific momentum conservation laws, both at differentiable and non-differentiable resolution scales, specific momentum conservation law associated with the differentiable–non-differentiable scale transition, etc.). In such a context, all results are explicated through analyzing biological processes, such as acute arterial occlusions as scale transitions. Thus, we show through a biophysical multifractal model that the blocking of the lumen of a healthy artery can happen as a result of the “stopping effect” associated with the differentiable-non-differentiable scale transition. We consider that blood entities move on continuous but non-differentiable (multifractal) curves. We determine the biophysical parameters that characterize the blood flow as a Bingham-type rheological fluid through a normal arterial structure assimilated with a horizontal “pipe” with circular symmetry. Our model has been validated based on experimental clinical data.     

Interpretable clustering using unsupervised binary trees

We herein introduce a new method of interpretable clustering that uses unsupervised binary trees. It is a three-stage procedure, the first stage of which entails a series of recursive binary splits to reduce the heterogeneity of the data within the new subsamples. During the second stage (pruning), consideration is given to whether adjacent nodes can be aggregated. Finally, during the third stage (joining), similar clusters are joined together, even if they do not share the same parent originally. Consistency results are obtained, and the procedure is used on simulated and real data sets.     

Green Polymer Chemistry VIII: Synthesis of Halo‐ester‐Functionalized Poly(ethylene glycol)s via Enzymatic Catalysis

Halo‐ester‐functionalized poly(ethylene glycol)s (PEGs) are successfully prepared by the transesterification of alkyl halo‐esters with PEGs using Candida antarctica lipase B (CALB) as a biocatalyst under the solventless conditions. Transesterifications of chlorine, bromine, and iodine esters with tetraethylene glycol monobenzyl ether (BzTEG) are quantitative in less than 2.5 h. The transesterification of halo‐esters with PEGs are complete in 4 h. ¹H and ¹³C NMR spectroscopy with MALDI‐ToF and ESI mass spectrometry confirm the structure and purity of the products. This method provides a convenient and “green” process to effectively produce halo‐ester PEGs.

     

Diorganotin(IV) dithiocarbamate complexes as chromogenic sensors of anion binding

One dinuclear chlorodiphenyltin (IV) dithiocarbamate complex (1) and four mononuclear complexes of general formula Ph₂Sn(S₂CNR)Cl (2, 3, 5, and 6) have been synthesized and characterized both in solid-state and solution. X-ray structures for complexes 1, 3 and 6 demonstrated a five-coordination geometry around of tin atoms, in which dithiocarbamate ligand chelates asymmetrically the metal center. As shown by ¹¹⁹Sn NMR spectroscopy, five-coordination geometry observed in the solid-state remains in solution. The stability of these chlorodiphenyltin(IV) dithiocarbamate complexes in the presence of biologically relevant anions such as acetate, dicarboxylates of general formula ^?OOC-(CH₂)_n-COO^? (n = 2–8), dihydrogenphosphate, hydrogensulfate, and halides has been examined in acetonitrile solutions. For all of these organotin(IV) complexes the displacement of the coordinated ligands (i.e., chloride and dithiocarbamate) from the organotin(IV) moiety occurred in the presence of monoanions like acetate, dihydrogenphosphate, hydrogensulfate and fluoride. A stepwise mechanism for ligand exchange is proposed based on UV–Vis, ¹H, ¹³C and ¹¹⁹Sn spectroscopic data, as well as mass spectrometry. From UV–Vis titration experiments it was found that dicarboxylates with small spacers like malonate and succinate, acted differently in the exchange of the dithiocarbamate group in comparison to other monoanionic O donor ligands or dicarboxylates with longer chains, perhaps by following an intramolecular displacement of the coordinated ligand.The lability of these organotin(IV) dithiocarbamate compounds in solution hampers their use as stably host for anions, however, by taking advantage of the intrinsic chromogenic properties of free dithiocarbamate anions, or by attaching dithiocarbamate groups to well-known fluorescent moieties such as antracene, these complexes can sense the presence of O-donor anions at very low concentrations by displacement of the metal-coordinated dithiocarbamate.     

Direct Analysis of Amphetamine Stimulants in a Whole Urine Sample by Atmospheric Solids Analysis Probe Tandem Mass Spectrometry

Amphetamine-type stimulants (ATS) are among illicit stimulant drugs that are most often used worldwide. A major challenge is to develop a fast and efficient methodology involving minimal sample preparation to analyze ATS in biological fluids. In this study, a urine pool solution containing amphetamine, methamphetamine, ephedrine, sibutramine, and fenfluramine at concentrations ranging from 0.5 pg/mL to 100 ng/mL was prepared and analyzed by atmospheric solids analysis probe tandem mass spectrometry (ASAP-MS/MS) and multiple reaction monitoring (MRM). A urine sample and saliva collected from a volunteer contributor (V1) were also analyzed. The limit of detection of the tested compounds ranged between 0.002 and 0.4 ng/mL in urine samples; the signal-to-noise ratio was 5. These results demonstrated that the ASAP-MS/MS methodology is applicable for the fast detection of ATS in urine samples with great sensitivity and specificity, without the need for cleanup, preconcentration, or chromatographic separation. Thus ASAP-MS/MS could potentially be used in clinical and forensic toxicology applications.

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Fluoroquinolones and sulfonamides: features of their determination in water. A review

Sulfonamides and fluoroquinolones are two group of antibiotics widely used in the treatment of bacterial infections. Monitoring these residues in live animals and animal products is commonly legislated; however, the environmental occurrence and fate is still sporadically assessed. The development of adequate analytical methods is a key issue to provide accurate data on concentrations of antimicrobial compounds and their residues in different organic matters. This review presents an overview of proposed methods published between 2008 and 2013 for analysis of fluoroquinolones and sulfonamides with special emphasis on sample preparation and detection systems employed. The coupling of high-performance liquid chromatography and mass spectrometry has been the most widely used method to determination of sulfonamides and fluoroquinolones, concomitantly to other antibiotics residues, due to high sensitivity and selectivity. The main drawbacks of this technique are the high cost and the equipment complexity. The coupling high-performance liquid chromatography and fluorescence detection has also been used to fluoroquinolones determination. Their fluorescent properties allowed the development of several methods with limits of detection in ng L^?1 range. Sample preparation is an important tool to reach lower detection limits and the online solid-phase extraction has a broader use. The hydrophilic–lipophilic balance polymeric are the mostly applied sorbents for sulfonamides and fluoroquinolones preconcentration. These sorbents have allowed reaching better recoveries and sensitivity improvement. Physico-chemical properties of these antibiotic groups in addition to trends on papers occurrence and frequency of analysis in different types of water (surface water, groundwater, drinking water and wastewater) are discussed.