Copper/Silver‐Mediated Direct ortho‐Ethynylation of Unactivated (Hetero)aryl CH Bonds with Terminal Alkyne

A copper/silver‐mediated oxidative ortho‐ethynylation of unactivated aryl C?H bonds with terminal alkyne has been developed. The reaction uses the removable PIP directing group and features broad substrate scope, high functional‐group tolerance, and compatibility with a wide range of heterocycles, providing an efficient synthesis of aryl alkynes. This procedure highlights the potential of copper catalysts to promote unique, synthetically enabling C?H functionalization reactions that lie outside of the current scope of precious metal catalysis.     

Dynamical transition for S‐K‐T biological competing model with cross‐diffusion

The main objective of this paper is to study the dynamical transition for the S‐K‐T biological competition system with cross‐diffusion. Based on the spectral analysis, the principle of exchange of stabilities conditions for eigenvalues are obtained. By using the dynamical transition theory, 2 different types of dynamical transition for the S‐K‐T model are also derived. In addition, an example is given to illustrate our main results.     

Development of a HPLC method for determination of four UV filters in sunscreen and its application to skin penetration studies

This study describes the development, validation and application of a high‐performance liquid chromatography (HPLC) method for the simultaneous determination of the in vitro skin penetration profile of four UV filters on porcine skin. Experiments were carried out on a gel‐cream formulation containing the following UV filters: diethylamino hydroxybenzoyl hexyl benzoate (DHHB), bis‐ ethylhexyloxyphenol methoxyphenyl triazine (BEMT), methylene bis‐ benzotriazolyl tetramethylbutylphenol (MBBT) and ethylhexyl triazone (EHT). The HPLC method demonstrated suitable selectivity, linearity (10.0–50.0 μg/mL), precision, accuracy and recovery from porcine skin and sunscreen formulation. The in vitro skin penetration profile was evaluated using Franz vertical diffusion cells for 24 h after application on porcine ear skin. None of the UV filters penetrated the porcine skin. Most of them stayed on the skin surface (>90%) and only BEMT, EHT and DHHB reached the dermis plus epidermis layer. These results are in agreement with previous results in the literature. Therefore, the analytical method was useful to evaluate the in vitro skin penetration of the UV filters and may help the development of safer and effective sunscreen products.     

Analytical challenges in quantifying abiraterone with LC–MS/MS in human plasma

A method was developed and validated to quantify abiraterone in human plasma. During assay development, several analytical challenges were encountered: limited stability in patient samples, adsorption to glass, coelution with metabolites and carry‐over issues. Limited stability (2 h) was found for abiraterone in fresh plasma as well as whole blood at ambient temperature. When kept at 2–8°C, abiraterone in plasma was stable for 24 h and in whole blood for 8 h. Adsorption of abiraterone to glass materials was addressed by using polypropylene throughout the method. Carry‐over was reduced to acceptable limits by incorporating a third mobile phase into the gradient. The chromatographic separation of abiraterone with its multiple metabolites was addressed by using a longer analytical column and adjusting the gradient. Abiraterone was extracted by protein precipitation, separated on a C18 column with gradient elution and analyzed with tandem quadrupole mass spectrometry in positive ion mode. A stable deuterated isotope was used as the internal standard. The assay ranges from 1 to 500 ng/mL. Within‐ and‐between‐day precisions and accuracies were below 13.4% and within 95–102%. This bioanalytical method was successfully validated and applied to determine plasma concentrations of abiraterone in clinical studies and in regular patient care for patients with metastatic castration‐resistant prostate cancer.     

Novel cyclodextrin‐modified h‐BN@Pd(II) nanomaterial: An efficient and recoverable catalyst for ligand‐free C‐C cross‐coupling reactions in water

An environmentally friendly palladium(II) catalyst supported on cyclodextrin‐modified h‐BN was successfully prepared. The catalyst was characterized by FT‐IR, SEM, TG, XRD and XPS, and the loading level of Pd in h‐BN@β‐CD@Pd(II) was measured to be 0.088 mmol g⁻¹ by ICP. It exhibits excellent catalytic activity for the Suzuki and Heck reactions in water, and can be easily separated and consecutively reused for at least nine times. In addition, a series of pharmacologically interesting products were successfully synthesized using this catalyst to demonstrate its potential applications in pharmaceutical industries. Above all, this work opens up an interesting and attractive avenue for the use of cyclodextrin‐functionalized h‐BN as an efficient support for hydrophilic heterogeneous catalysts.     

Identification and quantification of thymol metabolites in plasma,liver and duodenal wall of broiler chickens using UHPLC‐ESI‐QTOF‐MS

In the present study, we aimed to develop a method for thymol sulfate and thymol glucuronide determination in plasma, liver and duodenal wall of broiler chickens after feeding with a Thymus vulgaris essential oil at the different concentrations (0.01, 0.05 and 0.1% w /w). UHPLC coupled with accurate‐mass QTOF‐MS was used for identification and quantification of thymol metabolites. Novel Waters Oasis Prime HLB solid‐phase extraction cartridges were applied to sample clean‐up with extraction recoveries ranged from 85 to 92%. The presence of thymol glucuronide was confirmed by MS software according to molecular formula, score, mass error and double bond equivalent. In terms of validation, calibration curves of thymol sulfate were constructed in matrix samples with linearity from 3.91 to 250.0 ng/mL and correlation coefficients were within the range of 0.9979–0.9995. Limits of detection were 0.97, 0.29 and 0.63 ng/mL and limits of quantification were 3.23, 0.97 and 2.09 ng/mL for plasma, liver and duodenal wall, respectively. Intra‐day and inter‐day precision expressed as relative standard deviation were <4.35%. To highlight, thymol metabolites were directly detected for the first time in liver and duodenal wall and this method was shown to be successfully applicable for investigation of thymol metabolism in chickens after thyme essential oil ingestion.     

K(4P_J)-N_2,He碰撞转移及猝灭截面的测量

利用770nm脉冲激光激发基态K原子到K(4P1/2)态,在样品池中,利用原子荧光光谱方法,测量了K(4PJ)和N2、He碰撞的精细结构转移截面和碰撞猝灭截面。在不同N2、He气体密度下,通过对4P1/2→4S1/2共振荧光与4P3/2→4S1/2转移荧光的时间积分荧光强度进行测量,得到其荧光强度比与N2、He密度成线性关系。从荧光强度比R与(Nv)-1线性关系图中的直线斜率可以得到4P1/2→4P3/2转移截面为(2.77±0.69)×10-15cm2和4P3/2→4P1/2的碰撞转移截面为(1.62±0.41)×10-15cm2,从直线的截距计算出K(4P3/2)与N2、He的碰撞猝灭截面为(0.40±0.12)×10-15cm2和(0.60±0.18)×10-16cm2。     

Development and validation of an RP‐HPLC method for the quantitation of odanacatib in rat and human plasma and its application to a pharmacokinetic study

A simple, specific, sensitive and reproducible high‐performance liquid chromatography (HPLC) assay method has been developed and validated for the estimation of odanacatib in rat and human plasma. The bioanalytical procedure involves extraction of odanacatib and itraconazole (internal standard, IS) from a 200 μL plasma aliquot with simple liquid–liquid extraction process. Chromatographic separation was achieved on a Symmetry Shield RP₁₈ using an isocratic mobile phase at a flow rate of 0.7 mL/min. The UV detection wave length was 268 nm. Odanacatib and IS eluted at 5.5 and 8.6 min, respectively with a total run time of 10 min. Method validation was performed as per US Food and Drug Administration guidelines and the results met the acceptance criteria. The calibration curve was linear over a concentration range of 50.9–2037 ng/mL (r² = 0.994). The intra‐ and inter‐day precisions were in the range of 2.06–5.11 and 5.84–13.1%, respectively, in rat plasma and 2.38–7.90 and 6.39–10.2%, respectively, in human plasma. The validated HPLC method was successfully applied to a pharmacokinetic study in rats. Copyright © 2015 John Wiley & Sons, Ltd.