Development of an LC‐MS/MS method for determining the pharmacokinetics of clonidine following oral administration of Zhenju antihypertensive compound

Zhenju antihypertensive compound (ZJAHC) is a combined Chinese–Western medicine formula including clonidine (CLO), hydrochlorothiazide (HCT), rutin, Chrysanthemum indicum extract and pearl powder. Compared with CLO preparations, ZJAHC shows improved activities and decreased adverse effects. It is believed that the side effects of CLO are caused by its high peak plasma concentration. Hence, study of the influence of ZJAHC on the pharmacokinetic behaviors of clonidine seems essential. In present study, the plasma concentrations of CLO were determined with a liquid chromatography–tandem mass spectrometry (LC‐MS/MS) method. The MS/MS transitions monitored for clonidine and internal standard were 230.2 → 213.1 and 152.2 → 110.2, respectively. The analyte was quantified in a single run within 3 min. The pharmacokinetic study showed that the area under the plasma concentration–time curve of CLO in ZJAHC (60 µg/kg CLO) was similar to that of CLO‐HCT‐high (120 µg/kg CLO) but the peak concentration was much lower than that in CLO‐HCT‐high. ZJAHC could enhance the bioavailability without greatly increasing peak concentration of clonidine. This comprehensive effect of enhancing the bioavailability and avoiding the high peak plasma concentration for CLO might mainly result from the co‐contribution of Western medicine and traditional Chinese medicine (TCM), while the effect of TCM was stronger than that of Western medicine. Copyright © 2014 John Wiley & Sons, Ltd.     

Directing-Group-Free C7-Alkylations of N-Alkylindoles Mediated by Cationic Zirconium Complexes: Role of Brønsted Acid for Catalytic Manifold

Highly position selective alkylations of N-alkylindoles at C7-positions have been enabled by cationic zirconium complexes. The strategy provides a straightforward access to install alkyl groups at C7-positions of indoles without a complex directing group. Mechanistic studies provided support for the importance of Brønsted acids in the catalytic manifold.     

Unlocking the Drug Potential of the Bryostatin Family: Recent Advances in Product Synthesis and Biomedical Applications

Bryostatins are a class of naturally occurring macrocyclic lactones with a unique fast developing portfolio of clinical applications, including treatment of AIDS, Alzheimer's disease, and cancer. This comprehensive account summarizes the recent progress (2014–present) in the development of bryostatins, including their total synthesis and biomedical applications. An emphasis is placed on the discussion of bryostatin 1 , the most-studied analogue to date. This review highlights the synthetic and biological challenges of bryostatins and provides an outlook on their future development.     

Dynamic effect of constant inertial acceleration on vibration isolation system with high-order stiffness and Bouc–Wen hysteresis

Nonlinear Dynamics - Nonlinear vibration isolation provides with an effective way for vibration reduction with broad band and high efficiency. This investigation focuses on the dynamic effects of a...     

General Formation of Macro-/Mesoporous Nanoshells from Interfacial Assembly of Irregular Mesostructured Nanounits

Mesoporous core–shell nanostructures with controllable ultra-large open channels in their nanoshells are of great interest. However, soft template-directed cooperative assembly to mesoporous nanoshells with highly accessible pores larger than 30 nm, or even above 50 nm into macroporous range, remains a significant challenge. Herein we report a general approach for precisely tailored coating of hierarchically macro-/mesoporous polymer and carbon shells, possessing highly accessible radial channels with extremely wide pore size distribution from ca. 10 nm to ca. 200 nm, on diverse functional materials. This strategy creates opportunities to tailor the interfacial assembly of irregular mesostructured nanounits on core materials and generate various core–shell nanomaterials with controllable pore architectures. The obtained Fe,N-doped macro-/mesoporous carbon nanoshells show enhanced electrochemical performance for the oxygen reduction reaction in alkaline condition.     

Numerical Evaluation of a Two-Loop Diagram in the Cutoff Regularization

The sunset diagram of λφ4 theory is evaluated numerically in cutoff scheme and a nonzero finite term(in accordance with dimensional regularization (DR) result) is found in contrast to published calculations. This findingdramatically reduces the critical couplings for symmetry breaking in the two-loop effective potential discussed in ourprevious work.     

ON A PAIR OF NON-ISOMETRIC ISOSPECTRAL DOMAINS WITH FRACTAL BOUNDARIES AND THE WEYL-BERRY CONJECTURE

ＯＮＡＰＡＩＲＯＦＮＯＮＩＳＯＭＥＴＲＩＣＩＳＯＳＰＥＣＴＲＡＬＤＯＭＡＩＮＳＷＩＴＨＦＲＡＣＴＡＬＢＯＵＮＤＡＲＩＥＳＡＮＤＴＨＥＷＥＹＬＢＥＲＲＹＣＯＮＪＥＣＴＵＲＥＳＬＥＥＭＡＮ，Ｂ．Ｄ．ＣＨＥＮＨＵＡＭａｎｕｓｃｒｉｐｔｒｅｃ...     

从培养能力的角度看设计性实验

针对传统实验那种安排过死、刻板机械的特点，把设计性实验运用于教具设计与制作课程之中，充分地培养了学生动手、动脑的综合能力。     

氢化丁苯共聚物结构的核磁共振波谱表征Ⅱ.微观结构的定量计算

在氢化丁苯共聚物¹³C-NMR谱脂肪碳部分谱带归属的基础上,根据各谱带的主要来源,推导出六个二单元浓度的计算公式。计算出二单元、一单元的相对含量,各结构单元的数均序列长度、嵌段含量和其它结构参数。加氢前后的¹H-和¹³C-NMR谱的组成计算结果基本一致。初步探讨了作为粘度指数改进剂的氢化丁苯共聚物微观结构与性能的关系,为合成提供了依据。