Salting‐out‐assisted liquid–liquid extraction with acetonitrile for the determination of trimetazidine in rat plasma using liquid chromatography–mass spectrometry

A high‐throughout bioanalytical method based on salting‐out‐assisted liquid/liquid extraction (SALLE) method with acetonitrile and mass spectrometry‐compatible salts followed by LC‐MS/MS analysis of trimetazidine in rat plasma is presented. It required only 50 μL of plasma and allows the use of minimal volumes of organic solvents. The seamless interface of SALLE and LC‐MS eliminated the drying‐down step and the extract was diluted and injected into an LC‐MS/MS system with a cycle time of 2.5 min/sample. The retention times of trimetazidine and IS were approximately 1.1 and 1.7 min, respectively. Calibration curves were linear over the concentration range of 0.1–100 ng/mL, which can be extended to 500 ng/mL by dilution. The intra‐ and inter‐batch precision, accuracy and the relative standard deviation were all <15%. This method was successfully applied to determine trimetazidine concentrations in rat plasma. Copyright © 2014 John Wiley & Sons, Ltd.     

Metabolic profiles of dioscin in rats revealed by ultra‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry

Dioscin (DIS), one of the most abundant bioactive steroidal saponins in Dioscorea sp., is used as a complementary medicine to treat coronary disease and angina pectoris in China. Although the pharmacological activities and pharmacokinetics of DIS have been well demonstrated, information regarding the final metabolic fates is very limited. This study investigated the in vivo metabolic profiles of DIS after oral administration by ultra‐performance liquid chromatography quadrupole time‐of‐flight mass spectrometry method. The structures of the metabolites were identified and tentatively characterized by means of comparing the molecular mass, retention time and fragmentation pattern of the analytes with those of the parent compound. A total of eight metabolites, including seven phase I and one phase II metabolites, were detected and tentatively identified for the first time. Oxidation, deglycosylation and glucuronidation were found to be the major metabolic processes of the compound in rats. In addition, a possible metabolic pathway on the biotransformation of DIS in vivo was proposed. This study provides valuable and new information on the metabolism of DIS, which will be helpful for further understanding its mechanism of action. Copyright © 2015 John Wiley & Sons, Ltd.     

浮升力和流动加速对超临界CO2管内流动传热影响

基于单相流体的概念,超临界流体的异常传热行为已经被研究很多年了,但是关于其流动传热机理仍没有统一的认识.本文通过理论分析和实验研究了超临界二氧化碳在竖直管内向上流动过程中,浮升力和流动加速效应对其流动结构和传热过程的影响.结果表明,没有确凿的实验证据表明超临界流体的异常传热行为是浮升力和流动加速直接导致的,存在的估计浮升力和流动加速效应准则均是在常物性流体的基础上,做了大量假设得出的,不同的研究者采用浮升力和流动加速准则分析超临界流体的传热恶化得出的结论不一致.最后,基于拟沸腾理论分析超临界流体的传热恶化过程,提出超临界沸腾数区分了超临界流体正常传热与恶化传热的转换边界,为超临界流体流动传热研究提供新思路,超临界沸腾数对建立用于不同技术的超临界流体动力循环的最佳运行条件具有重要意义.     

New Phenomena in Organometallic‐Mediated Radical Polymerization (OMRP) and Perspectives for Control of Less Active Monomers

The impact of reversible bond formation between a growing radical chain and a metal complex (organometallic‐mediated radical polymerization (OMRP) equilibrium) to generate an organometallic intermediate/dormant species is analyzed with emphasis on the interplay between this and other one‐electron processes involving the metal complex, which include halogen transfer in atom transfer radical polymerization (ATRP), hydrogen‐atom transfer in catalytic chain transfer (CCT), and catalytic radical termination (CRT). The challenges facing the controlled polymerization of “less active monomers” (LAMs) are outlined and, after reviewing the recent achievements of OMRP in this area, the perspectives of this technique are analyzed.     

Zinc polyoxometalate on activated carbon: an efficient catalyst for selective oxidation of alcohols with hydrogen peroxide

[PW₁₁ZnO₃₉]^5? was immobilized on activated carbon and characterized using Fourier transform infrared, X‐ray diffraction, Brunauer–Emmett–Teller and elemental analysis techniques. Effective oxidation of various alcohols with hydrogen peroxide was performed in the presence of this catalyst. Easy separation of the catalyst from the reaction mixture, cheapness, high activity and selectivity, stability as well as retained activity in subsequent catalytic cycles make this supported catalyst suitable for small‐scale synthesis. Copyright © 2015 John Wiley & Sons, Ltd.     

Doxorubicin Encapsulation in Carbon Nanotubes Having Haeckelite or Stone–Wales Defects as Drug Carriers: A Molecular Dynamics Approach

Doxorubicin (DOX), a recognized anticancer drug, forms stable associations with carbon nanotubes (CNTs). CNTs when properly functionalized have the ability to anchor directly in cancerous tumors where the release of the drug occurs thanks to the tumor slightly acidic pH. Herein, we study the armchair and zigzag CNTs with Stone–Wales (SW) defects to rank their ability to encapsulate DOX by determining the DOX-CNT binding free energies using the MM/PBSA and MM/GBSA methods implemented in AMBER16. We investigate also the chiral CNTs with haeckelite defects. Each haeckelite defect consists of a pair of square and octagonal rings. The armchair and zigzag CNT with SW defects and chiral nanotubes with haeckelite defects predict DOX-CNT interactions that depend on the length of the nanotube, the number of present defects and nitrogen doping. Chiral nanotubes having two haeckelite defects reveal a clear dependence on the nitrogen content with DOX-CNT interaction forces decreasing in the order 0N > 4N > 8N. These results contribute to a further understanding of drug-nanotube interactions and to the design of new drug delivery systems based on CNTs.     

Chromatography-Free Multicomponent Synthesis of Thioureas Enabled by Aqueous Solution of Elemental Sulfur

The development of a new three-component chromatography-free reaction of isocyanides, amines and elemental sulfur allowed us the straightforward synthesis of thioureas in water. Considering a large pool of organic and inorganic bases, we first optimized the preparation of aqueous polysulfide solution from elemental sulfur. Using polysulfide solution, we were able to omit the otherwise mandatory chromatography, and to isolate the crystalline products directly from the reaction mixture by a simple filtration, retaining the sulfur in the solution phase. A wide range of thioureas synthesized in this way confirmed the reasonable substrate and functional group tolerance of our protocol.     

Simultaneous quantification of leukotrienes and hydroxyeicosatetraenoic acids in cell culture medium using liquid chromatography/tandem mass spectrometry

Leukotrienes (LTs) and hydroxyeicosatetraenoic acids (HETEs) are important bioactive lipid mediators that participate in various pathophysiological processes. To advance understanding of the mechanisms that regulate these mediators in physiological and pathological processes, an analytical method using liquid chromatography/tandem mass spectrometry for the simultaneous quantification of LTB₄, LTC₄, LTD₄, LTE₄, 5‐HETE_, 8‐HETE, 12‐HETE and 15‐HETE in cell culture media was developed. A Supel?‐Select HLB solid‐phase extraction cartridge was used for sample preparation. The compounds were separated on a C₁₈ column using gradient elution with acetonitrile–water–formic acid (20:80:0.1, v/v/v) and acetonitrile–formic acid (100:0.1, v/v). The calibration curves of LTB₄, LTD₄, LTE₄ and HETEs were linear in the range of 0.025–10 ng/mL, and the calibration curve of LTC₄ was linear in the range of 0.25–10 ng/mL. Validation assessment showed that the method was highly reliable with good accuracy and precision. The stability of LTs and HETEs was also investigated. Using the developed method, we measured LTs and HETEs in the culture supernatant of the human mast cell line HMC‐1. The present method could facilitate investigations of the mechanisms that regulate the production, release and signaling of LTs and HETEs. Copyright © 2014 John Wiley & Sons, Ltd.     

Thermally induced solid-state transformation of cimetidine. A multi-spectroscopic/chemometrics determination of the kinetics of the process and structural elucidation of one of the products as a stable N3-enamino tautomer

Exposure of cimetidine (CIM) to dry heat (160–180 °C) afforded, upon cooling, a glassy solid containing new and hitherto unknown products. The kinetics of this process was studied by a second order chemometrics-assisted multi-spectroscopic approach. Proton and carbon-13 nuclear magnetic resonance (NMR), as well as ultraviolet and infrared spectroscopic data were jointly used, whereas multivariate curve resolution with alternating least squares (MCR-ALS) was employed as the chemometrics method to extract process information. It was established that drug degradation follows a first order kinetics.     

An Improved Composite Multiscale Fuzzy Entropy for Feature Extraction of MI-EEG

Motor Imagery Electroencephalography (MI-EEG) has shown good prospects in neurorehabilitation, and the entropy-based nonlinear dynamic methods have been successfully applied to feature extraction of MI-EEG. Especially based on Multiscale Fuzzy Entropy (MFE), the fuzzy entropies of the τ coarse-grained sequences in τ scale are calculated and averaged to develop the Composite MFE (CMFE) with more feature information. However, the coarse-grained process fails to match the nonstationary characteristic of MI-EEG by a mean filtering algorithm. In this paper, CMFE is improved by assigning the different weight factors to the different sample points in the coarse-grained process, i.e., using the weighted mean filters instead of the original mean filters, which is conductive to signal filtering and feature extraction, and the resulting personalized Weighted CMFE (WCMFE) is more suitable to represent the nonstationary MI-EEG for different subjects. All the WCMFEs of multi-channel MI-EEG are fused in serial to construct the feature vector, which is evaluated by a back-propagation neural network. Based on a public dataset, extensive experiments are conducted, yielding a relatively higher classification accuracy by WCMFE, and the statistical significance is examined by two-sample t-test. The results suggest that WCMFE is superior to the other entropy-based and traditional feature extraction methods.