Synthesis of Potential Impurities of Bicalutamide

Bicalutamide is an oral nonsteroidal, anti-androgen drug used for prostate cancer. It binds to the androgen receptor. During the bulk synthesis of bicalutamide, various impurities are formed. The present work details the development of simple processes for the preparation of impurities of bicalutamide, viz bical-sulfoxides (6), bical-deshydroxy (10), bical-desfluoro (10a), bical-2-fluoro (10b), and bical-3-fluoro (10c).     

用激光吹气注入高Z杂质使HL-1M托卡马克放电安全终止的研究

采用高Z杂质注入HL-1M等离子体中, 触发等离子体电流衰竭的实验已经施行.用激光吹气注入高Z杂质能够增加辐射冷却，等离子体在-3ms时间内迅速冷却而且在电流终止之前电子温度损失约80%.实验证明：它是一种使得大型聚变实验装置上在放电破裂之前显著减少等离子体中热能而且安全终止放电的简单、快速和有效的途径. 关键词： 高Z杂质 破裂 等离子体终止 激光吹气     

Life‐cycle toxicity of dibutyltin to the sheepshead minnow (Cyprinodon variegatus) and implications of the ubiquitous tributyltin impurity in test material

Dibutyltin (DBT) is used in the plastics polymerization process as a catalyst in polyvinyl chloride (PVC) products and is the primary degradation product of tributyltin (TBT), an antifoulant in marine paint. DBT and other organotin compounds make their way into the environment through antifoulants, PVC processing plants, and PVC products maintained in water and water‐handling systems. A flow‐through saltwater life‐cycle toxicity test was conducted to determine the chronic effect of DBT to the sheepshead minnow (Cyprinodon variegatus Lacepede), an estuarine species. Embryos were monitored through hatch, maturation, growth, and reproduction in DBT concentrations of 158, 286, 453, 887, and 1510 µg l^?1. Progeny were monitored for survival as embryos and fry/juveniles, and growth for 30 days post‐isolation. Mean length of parental generation fish was significantly reduced on day 30 at DBT concentrations ≥887 µg l^?1, setting the lowest observable effect concentration (LOEC) at 887 µg l^?1 and the no observable effect concentration (NOEC) at 453 µg l^?1. Fecundity, as egg viability, was significantly reduced at the LOEC. Survival of parental and progeny generation embryos and mean length, wet weight and dry weight of progeny generation juveniles were not significantly affected at concentrations ≤LOEC. TBT, a toxic impurity in DBT reversibly produced in DBT by the process of comproportionation, was also monitored throughout this study. Comparing measured levels of TBT in this study with levels exerting toxic effects in an earlier TBT life‐cycle study with C. variegatus suggests biological responses in this study were likely due to the TBT impurity and not to DBT alone. Results indicate that TBT impurity as low as 0.1% may have a significant influence on the perceived toxicity of DBT and that spontaneous production of TBT in DBT may be the major source of biological toxicity of DBT. Copyright © 2003 John Wiley & Sons, Ltd.     

Luminescent impurity doping trends in alternating-current thin-film electroluminescent phosphors

The doping properties of three alternating-current thin-film electroluminescent (ACTFEL) phosphor host/luminescent impurity systems, ZnS:Mn, SrS:Ce, and SrS:Cu, are elucidated, and the ACTFEL device implications of these properties are assessed. Mn is isovalent, Ce is a donor, and Cu is an acceptor. Moreover, Ce is readily ionized in SrS, so that it behaves as a double donor. The distinctly different doping nature of these three luminescent impurities leads to dramatically disparate defect and device physics trends. The donor/acceptor nature of Ce/Cu in SrS results in charge neutrality being achieved in SrS:Ce and SrS:Cu via self-compensation-induced vacancy creation; subsequent defect complexing between oppositely charged luminescent impurities and self-compensation-induced vacancies results in more complex ACTFEL device behaviors such as dynamic space charge, trailing-edge emission, charge collapse, color tuning, and electroluminescence (EL) thermal quenching. In contrast, the isovalent nature of ZnS:Mn leads to more ideal ACTFEL device operation. This suggests that the optimal ACTFEL phosphor luminescent impurity is isovalent.     

Critical investigation of coupled liquid chromatography–NMR spectroscopy in pharmaceutical impurity identification

In this paper, we investigate the application of coupled LC–NMR to the identification of low‐level impurities. We consider the absolute sensitivity of the technique with our instrumentation, and how this is degraded by peak broadening on and after column, and we compare the sensitivity and other aspects of LC–NMR with a more classical approach of impurity isolation and tube NMR. We show that despite the undoubted advantages of LC–NMR in many situations, for the identification of very low‐level impurities it may not always be the most efficient overall approach when all factors are considered. Copyright © 2003 John Wiley & Sons, Ltd.     

Isolation and characterization of degradation products of citalopram and process-related impurities using RP-HPLC

A reversed-phase high-performance liquid chromatographic method for simultaneous separation and determination of citalopram hydrobromide and its process impurities in bulk drugs and pharmaceutical formulations was developed. The separation was accomplished on an Inertsil ODS 3V (250x4.6 mm; particle size 5 mum) column using 0.3% diethylamine (pH = 4.70) and methanol/acetonitrile (55:45 v/v) as mobile phase in a gradient elution mode. The eluents were monitored by a photodiode array detector set at 225 nm. The chromatographic behavior of all the related substances was examined under variable conditions of different solvents, buffer concentrations, and pH. The method was validated in terms of accuracy, precision, and linearity. The method could be of use not only for rapid and routine evaluation of the quality of citalopram in bulk drug manufacturing units but also for the detection of its impurities in pharmaceutical formulations. Three unknown impurities were consistently observed during the analysis of different batches of citalopram. Forced degradation of citalopram was carried out under thermal, photo, acidic, alkaline, and peroxide conditions. The degradation products and unknown impurities were isolated and characterized by ESI-MS/MS, (1)H NMR, and FT-IR spectroscopy.     

Synthesis and characterization of potential impurities of Oxcarbazepine drug substance: An antiepileptic agent

Oxcarbazepine is a drug substance used to treat epilepsy. During its bulk synthesis of various impurities formation will be observed. Herein we describe the formation, synthesis and characterization of four potential impurities, namely, N-acetyl Oxcarbazepine, N-formyl Oxcarbazepine, N-carbamoyl Oxcarbazepine, and Oxcarbazepine dimer. These impurities are listed in several Pharmacopoeias and the control of these impurities below the threshold level is essential. Our study will be a guide for making these reference standards.     

Surface and grain boundary segregation in 16MND5 steel

An adequate model of quantification when there are many segregating elements is required for industry and research. Hence, for the first time, surface segregation kinetics on industrial 16MND5 steel was studied by XPS spectroscopy at temperatures ranging from 500 to 600 ^oC. From measurements that highlight the competitive segregation of P, S, Sn, Sb, As, and Cu impurities at the surface, a quantification model was developed and successfully used to deduce the surface concentrations during segregation kinetics as well as derive the corresponding diffusion coefficients. We observed that phosphorus and sulfur are the first elements covering the surface, then they are supplanted by others' impurities. This result may reflect impurities segregation behavior at the grain boundaries that impacts mechanical behavior of the material. Indeed, to further the research, 16MND5 samples were aged in the same range of temperatures. Then, Auger spectroscopy measurements at grain boundaries were conducted on broken samples exhibiting intergranular cracking. Results show that phosphorus is the only segregating element present at grain boundaries after 2 months of aging. Importantly, it appears that phosphorus grain boundary segregation kinetics is significantly lower than at surface. Copyright © 2017 John Wiley & Sons, Ltd.     

Carbocatalysis: The State of “Metal‐Free” Catalysis

The rise in global demand for crucial chemical compounds has driven immense research in the fundamental science of catalysis. Graphene and its derivatives (chemically modified graphene, CMGs) have recently emerged as a new class of heterogeneous catalyst that promises economically viable and greener routes to these compounds. Although CMGs possess unique catalytic properties, the actual active sites are often points of discussion. Current minimal understanding on the possible effects of metallic impurities on the electrocatalytic performances of these CMGs calls forth the need to raise awareness on possible metallic impurities misrepresenting the actual chemical catalytic performances of the CMGs. This Minireview highlights the latest advances in the application of CMGs as catalysts, with an emphasis on the possible effects of metallic impurities on CMG catalysis.