Development of a bioanalytical method for the quantification of sinococuline in human plasma and its application in phase I clinical pharmacokinetic study

A selective, highly sensitive, precise, and novel bioanalytical method has been developed and validated to quantify sinococuline, an active constituent present in the phytopharmaceutical drug product containing Cocculus hirsutus plant extract, in vivo. Chromatographic separation was achieved on a Luna Omega Polar-C18 bonded analytical column maintained at 45°C. The isocratic mobile phase consisted of methanol and ammonium formate buffer (60:40, v/v) at acidic pH with a low flow rate of 0.250 mL/min. Detection was performed on an API 4000 mass spectrometer using electrospray ionization in positive polarity and multiple reaction monitoring mode to achieve a lower limit of quantification of 1.50 ng/mL. Excellent accuracy and precision were obtained after extracting the analyte from plasma samples using a chemical analogue as an internal standard in the absence of an isotope-labeled compound. The extraction efficacy was evidenced from recovery study, and the analyte was found to be stable in plasma. Validation study demonstrated linearity with coefficient of correlation, r ≥ 0.99, and minimal matrix effect. This bioanalytical method was successfully applied to evaluate pharmacokinetic parameters of sinococuline from a phase I clinical trial of an aqueous extract of C. hirsutus in healthy human volunteers.     

Functional Groups Assisted Tunable Dielectric Permittivity of Guest-Free Zn-Based Coordination Polymers for Gate Dielectrics

The dielectric properties of coordination polymers has been a topic of recent interest, but the role of different functional groups on the dielectric properties of these polymers has not yet been fully addressed. Herein, the effects of electron-donating (R=NH₂) and electron-withdrawing (R=NO₂) groups on the dielectric behavior of such materials were investigated for two thermally stable and guest-free Zn-based coordination polymers, [Zn(L₁)(L₂)]_n ( 1 ) and [Zn(L₁)(L₃)]_n ( 2 ) [L₁=2-(2-pyridyl) benzimidazole (Pbim), L₂=5-aminoisophthalate (Aip), and L₃=5-nitroisophthalate (Nip)]. The results of dielectric studies of 1 revealed that it possesses a high dielectric constant (κ=65.5 at 1 kHz), while compound 2 displayed an even higher dielectric constant (κ=110.3 at 1 kHz). The electron donating and withdrawing effects of the NH₂ and NO₂ substituents induce changes in the polarity of the polymers, which is due to the inductive effect from the aryl ring for both NO₂ and NH₂. Theoretical results from density functional theory (DFT) calculations, which also support the experimental findings, show that both compounds have a distinct electronic behavior with diverse wide bandgaps. The significance of the current work is to provide information about the structure-dielectric property relationships. So, this study promises to pave the way for further research on the effects of different functional groups on coordination polymers on their dielectric properties.     

Superquantiles at Work: Machine Learning Applications and Efficient Subgradient Computation

Set-Valued and Variational Analysis - R. Tyrell Rockafellar and his collaborators introduced, in a series of works, new regression modeling methods based on the notion of superquantile (or...     

Experimental and numerical analysis of cylindrical turbulators in a double pipe heat exchanger under turbulent flow conditions

In the present work, the use of cylindrical turbulators in a double pipe heat exchanger has been investigated. Cylindrical fin type of turbulators has been placed circumferentially separated by 90° on the outer side of an inner pipe at a regular pitch. Experimental studies were undertaken for different air flow rates in a turbulent regime whose Reynolds number range between 2500 and 10000. Heat transfer characteristics like Nu and friction factor have been experimentally determined. Parametric studies were conducted by changing the pitch and also the orientation of the turbulators. Nu and friction factor were found to increase as the pitch is reduced. A model with alternatively changed orientation outperformed others by exhibiting highest Nu and reduced friction factor.     

Development and Validation of LC-ESI-MS/MS Method for the Determination of Alfuzosin in Human Plasma

Journal of Analytical Chemistry - A new liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method has been developed and validated for alfuzosin quantification in...     

An M/G/1 Retrial Queueing System with Two-Phase Service and Preemptive Resume

An M/G/1 retrial queueing system with additional phase of service and possible preemptive resume service discipline is considered. For an arbitrarily distributed retrial time distribution, the necessary and sufficient condition for the system stability is obtained, assuming that only the customer at the head of the orbit has priority access to the server. The steady-state distributions of the server state and the number of customers in the orbit are obtained along with other performance measures. The effects of various parameters on the system performance are analysed numerically. A general decomposition law for this retrial queueing system is established.     

Forced-air precooling of spherical foods in bulk: A parametric study

In this paper, a mathematical model for forced-air precooling of spherical food products in bulk is developed. The foods are arranged in horizontal layers stacked one above the other to form a rectangular parallelepiped with a vertical gap in between the product layers. The foods are cooled by chilled air blown along the height of the package. The governing equations for the conduction heat transfer in the foods, simultaneous heat and mass transfer at the food-air interface and in the air stream are solved numerically using finite-difference methods. A comprehensive numerical study is performed by varying the process parameters over a wide range. Typical results showing the variation of moist air properties along the height of the package and the effect of each parameter on the process time are presented. The ranges of parameters for advantageous operation of the precooling system are identified. Correlations are obtained for the process time based on the product center and mass-averaged temperatures in terms of process parameters.     

A ring-closing metathesis approach to a synthesis of the B ring of eleutherobin

A short and efficient RCM route is reported for the construction of the key nine-membered B ring of eleutherobin starting from the readily available 1,2,5,6-diisopropylidene-d-glucose.     

Dioxouranium(VI) mixed ligand complexes containingo-substituted benzoic acid and α-amino acids

Summary Mixed ligand complexes of general formula [UO₂L¹L²-(H₂O)_n], where L¹ iso-hydroxy-,o-mercapto- oro-aminobenzoic acid and L² is glycine, L-alanine, or L-valine, have been prepared and characterized. The uranium atom in these complexes is 6- or 8-coordinate. Both acid ligands are bidentate, bonding through the ionized –COO^–– group and either O, N or S atoms.