Dose‐dependent exposure profile and metabolic characterization of notoginsenoside R1 in rat plasma by ultra‐fast liquid chromatography–electrospray ionization–tandem mass spectrometry

Notoginsenoside R₁ (NGR₁), a diagnostic protopanaxatriol‐type (ppt‐type) saponin in Panax notoginseng, possesses potent biological activities including antithrombotic, anti‐inflammatory, neuron protection and improvement of microcirculation, yet its pharmacokinetics and metabolic characterization as an individual compound remain unclear. The aim of this study was to investigate the exposure profile of NGR₁ in rats after oral and intravenous administration and to explore the metabolic characterization of NGR₁. A simple and sensitive ultra‐fast liquid chromatographic–tandem mass spectrometric method was developed and validated for the quantitative determination of NGR₁ and its major metabolites, and for characterization of its metabolic profile in rat plasma. The blood samples were precipitated with methanol, quantified in a negative multiple reaction monitoring mode and analyzed within 6.0 min. Validation parameters (linearity, precision and accuracy, recovery and matrix effect, stability) were within acceptable ranges. After oral administration, NGR₁ exhibited dose‐independent exposure behaviors with t_1/2 over 8.0 h and oral bioavailability of 0.25–0.29%. A total of seven metabolites were characterized, including two pairs of epimers, 20(R)‐notoginsenoside R₂/20(S)‐notoginsenoside R₂ and 20(R)‐ginsenoside Rh₁/20(S)‐ginsenoside Rh₁, with the 20(R) form of saponins identified for the first time in rat plasma. Five deglycometabolites were quantitatively determined, among which 20(S)‐notoginsenoside R₂, ginsenoside Rg₁, ginsenoside F₁ and protopanaxatriol displayed relatively high exploration, which may partly explain the pharmacodynamic diversity of ginsenosides after oral dose.     

Pharmacokinetics of salvianolic acid B,rosmarinic acid and Danshensu in rat after pulmonary administration of Salvia miltiorrhiza polyphenolic acid solution

A sensitive and accurate LC–MS/MS method was established for quantifying salvianolic acid B (Sal B), rosmarinic acid (Ros A) and Danshensu (DA) in rat plasma. Salvia miltiorrhiza polyphenolic acid (SMPA), active water‐soluble ingredients isolated and purified from Salvia miltiorrhiza Bge included Sal B, Ros A and DA. The pharmacokinetic analysis of Sal B, Ros A and DA after pulmonary administration of SMPA solution to rat was performed by LC–MS/MS. Results from the pharmacokinetic studies showed that the peak concentration of DA was 21.85 ± 6.43 and 65.39 ± 3.83 ng/mL after pulmonary and intravenous administration, respectively. DA was not detected at 2 h after administration. The absolute bioavailabilities of Sal B and Ros A were respectively 50.37 ± 27.04 and 89.63 ± 12.16% after pulmonary administration of 10 mg/kg SMPA solution in rats. The absolute bioavailability of Sal B increased at least 10‐fold after pulmonary administration, compared with oral administration. It was concluded that the newly established LC–MS/MS method was suitable for describing the pharmacokinetic characteristics of Sal B, Ros A and DA in rat after pulmonary administration of SMPA solution. The data from this study will provide a preclinical insight into the feasibility of pulmonary administration of SMPA.     

基于Voronoi切割算法的碎冰区构造及离散元分析

离散元方法广泛应用于海冰，特别是碎冰区的动力过程及其对海洋结构作用过程的数值模拟。为构造碎冰区中的冰块几何特性，基于二维Voronoi图方法对计算域进行随机切割以生成碎冰区中冰块的几何形态，并采用球体单元对每个碎冰块单元进行填充，从而确定碎冰区的初始分布场。在采用Voronoi图进行碎冰区构造时，可对冰块尺寸、几何形态和密集度等海冰参数进行设定。为确定冰块的不同几何规则度，综合采用排斥法和扰动法以定量地控制碎冰块几何形态从完全随机分布到规则分布的连续变换。为分析不同几何规则度下碎冰块的几何特性概率分布规律，对计算域内冰块的面积和边数等参数进行统计分析，从而可更合理地参数化控制初始冰场中碎冰块的几何特性。在此基础上，本文基于粘接-破碎的球体离散元方法对不同冰况下锥体结构的冰荷载进行了数值计算，讨论分析了碎冰区的海冰密集度、冰块面积和几何规则度对冰载荷的影响。     

Effect of ethanediamine on bio-polishing of cotton fabrics with cellulase

n-Propylamine and n-butylamine showed an inhibitory effect on cellulase A and cellulase B, while ethanediamine displayed a positive effect on both of these cellulases. Relative filter paper activity and relative CMCase activity of cellulase A and cellulase B measured at 50 °C were increased by 16.0 and 25.2 %, and 18.9 and 13.9 %, respectively, by the appearance of ethanediamine at a certain concentration. Also the addition of ethanediamine maintained the thermal stability of cellulase A and B at 65 °C to some extent and showed a stronger stabilizing effect on cellulase A than cellulase B. Third, the addition of ethanediamine within a certain concentration range enhanced the bio-polishing effect of cotton fabric enzymatic treatment at 50 °C to some extent, obtaining a close bio-polishing effect of cotton fabrics treated at 50 °C; the addition of ethanediamine saved some of the dose of cellulase A and B. Last but not least, the appearance of ethanediamine broadened the operating temperature of cellulase A to 65 °C, and it had a less positive effect on cellulase B at 65 °C.     

2,3,7,8,12,13-Hexakis[2-(2-methoxyethoxy)ethoxy]tricycloquinazoline: a discogen which allows enhanced levels of n-doping

A synthesis has been developed for 2,3,7,8,12,13-hexakis[2-(2-methoxyethoxy)ethoxy]-tricycloquinazoline (TCQ6EO2M) in which the ethylenoxy side chains are introduced before elaboration of the heterocylic core. This discogen gives a hexagonal columnar phase (Col_h) between 77 and 233°C. n-Doping using potassium metal is facilitated firstly by the electron poor/π-deficient nature of the core and secondly by the polyethylenoxy side chains which complex the potassium K⁺ counter-ions. The conductivity of the Col_h phase of TCQ6EO2M doped with 10 mol % potassium (σ _∥ = 1.1 x 10^-3 S m^-1) is substantially higher than that previously reported for 2,3,7,8,12,13-hexa(hexylthio)tricycloquinazoline doped with 6 mol % potassium (σ _∥ = 2.9 x 10^-5 S m^-1). Photoconductivity studies of TCQ6EO2M using a time of flight sample configuration show transient photocurrents for both holes and electrons. From these an upper limit on the mobility for the electrons is estimated as ~10^-4 cm² V^-1 s^-1 at 150°C which is of the same magnitude as that for hole mobilities in other columnar discotic liquid crystals.     

One-Pot Synthesis of 2-Arylthiazolines with 1-Butyl-3-Methylimidazolium Tribromide as a Catalytic Reagent

Abstract

A simple, inexpensive, and efficient one-pot synthesis of 2-arylthiazoline derivatives under solvent-free conditions using a catalytic amount of 1-butyl-3-methylimidazolium tribromide with excellent product yields is reported. This methodology provides easy, quantitative access to various 2-arylthiazoline derivatives, using environmentally benign 1-butyl-3-methylimidazolium tribromide as a catalyst.