Tuner design and RF test of a four-rod RFQ

A mini-vane four-rod radio frequency quadruple (RFQ) accelerator has been built for neutron imaging. The RFQ will operate at 201.5 MHz, and its length is 2.7 m. The original electric field distribution along the electrodes is not flat. The resonant frequency needs to be tuned to the operating value. And the frequency needs to be compensated for temperature change during high power RF test and beam test. As tuning such a RFQ is difficult, plate tuners and stick tuners are designed. This paper will present the tuners design, the tuning procedure, and the RF properties of the RFQ.

     

Development and validation of UPLC‐MS/MS method for determination of domperidone in human plasma and its pharmacokinetic application

A sensitive, rapid and selective ultra‐performance liquid chromatography–tandem mass spectrometric (UPLC‐MS/MS) method was developed for the determination and pharmacokinetic study of domperidone in human plasma. Diphenhydramine was used as the internal standard. Plasma sample pretreatment involved a one‐step liquid–liquid extraction with a mixture of diethyl ether–dichloromethane (3:2, v/v). The analysis was carried out on an Acquity UPLC^TM BEH C₁₈ column. The mobile phase consisted of methanol–water containing 10 mmol/L ammonium acetate and 0.5% (v/v) formic acid (60:40, v/v). The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring mode via electrospray ionizationsource with positive mode. Each plasma sample was chromatographed within 2.1 min. The standard curves for domperidone were linear (r² ≥ 0.99) over the concentration range of 0.030–31.5 ng/mL with a lower limit of quantification of 0.030 ng/mL. The intra‐ and inter‐day precision (relative standard deviation) values were not higher than 13% and accuracy (relative error) was from ?7.6 to 1.2% at three quality control levels. The method herein described was superior to previous methods and was successfully applied to the pharmacokinetic study of domperidone in healthy Chinese volunteers after oral administration. Copyright © 2012 John Wiley & Sons, Ltd.     

Evaluation of approximations for concentration-dependent micropore diffusion in sorbent with bidisperse pore structure

Average diffusivity linear driving force (AD-LDF) and concentration-dependent diffusivity linear driving force (CDD-LDF) approximations are introduced to simplify the precise model describing the concentration-dependent micropore diffusion in bidisperse sorbents, and are compared with the precise model in predicting the dynamics of a sorption process under two different perturbations (i.e., step change perturbations and sinusoidal wave perturbation) with different concentrations imposed at the exterior surface of the bidisperse sorbent. The performance of the two approximations is validated by the precise model and experiments. The AD-LDF performs better in step adsorption and CDD-LDF does better in step desorption. Under sinusoidal wave perturbation, the CDD-LDF performs better. The different levels of consistency of the two approximations with the precise model are attributed to the different definitions of the diffusivities.     

Design,synthesis and biological evaluation of pyridyl substituted benzoxazepinones as potent and selective inhibitors of aldosterone synthase

Exorbitant aldosterone is closely associated with various severe diseases, including congestive heart failure and chronic kidney disease. As aldosterone synthase is the pivotal enzyme in aldosterone biosynthesis, its inhibition constitutes a promising treatment for these diseases. Via a structure-based approach, a series of pyridyl substituted 3,4-dihydrobenzo[f][1,4]oxazepin-5(2H)-ones were designed as inhibitors of aldosterone synthase. Six compounds (5j, 5l, 5m 5w, 5x and 5y) distinguished themselves with potent inhibition (IC₅₀ <100 nmol/L) and high selectivity over homogenous 11β-hydroxylase. As the most promising compound, 5x exhibited an IC₅₀ of 12 nmol/L and an excellent selectivity factor (SF) of 157, which are both superior to those of the reference fadrazole (IC₅₀ = 21 nmol/L, SF = 7). Importantly, 5x showed no inhibition against steroidogenic CYP17, CYP19 and a panel of hepatic CYP enzymes indicating an outstanding safety profile. As it manifested satisfactory pharmacokinetic properties in rats, compound 5x was considered as a drug candidate for further development.