A Rapid and Sensitive LC–MS Method for Determination of Ezetimibe Concentration in Human Plasma: Application to a Bioequivalence Study

A selective and highly sensitive high performance liquid chromatography-electrospray ionization mass spectrometry method has been developed for determination of ezetimibe concentrations in human plasma. Ezetimibe was extracted from plasma with ethyl acetate followed by evaporation of the organic layer and, then, reconstitution of the residue in mobile phase before injection to chromatograph. The mobile phase consisted of acetonitrile-ammonium acetate (10 mM, pH 3.0), 75:25 (v/v). An aliquot of 10 μL was chromatographically analyzed on a prepacked Zorbax XDB-ODS C₁₈ column (2.1 × 100 mm, 3.5 micron). Detection of analytes was achieved by mass spectrometry with atmospheric pressure chemical ionization (APCI) interface in the negative ion mode operated under the multiple-reaction monitoring mode (m/z transition: ezetimibe 408–271). Standard curves were linear (r = 0.998) over the wide ezetimibe concentration range of 0.05–30.0 ng mL⁻¹ with acceptable accuracy and precision. The limit of detection was 0.02 ng mL⁻¹. The validated LC–APCI–MS method has been used successfully throughout a bioequivalence study on an ezetimibe generic product in 24 healthy male volunteers.

     

Synthesis,Characterization and Properties of a Novel Environmentally Friendly Mono Azo Disperse Dye and Its Application on Polyethylene Terephthalate (PET)

The aim of this research is to achieve the synthesis of a novel mono azo disperse dye containing both a β‐naphthyl acetate group and carboxylic acid ester group and application on PET fabric. In this study the dyeing properties have also been investigated. The synthesized dye was characterized using UV‐Vis, FTIR, ¹H NMR and ¹³C NMR spectroscopic techniques. To investigate alkali‐clearability, both alkali‐hydrolysis behavior and the effect of its fastness properties with regard to PET fabric were examined. This dye showed a reasonable level of hydrolysis under relatively mild alkaline conditions. The application of the dye to PET fabric showed good leveling and building up properties. Estimating fastness properties of the dyed fabric showed excellent wash, rubbing fastness, good light and sublimation fastness. The results furthermore displayed that the synthesized dye offers the option of alkali‐clearing process over that of a conventional reduction‐clearing process. Therefore, the value of Chemical Oxygen Demand (COD), Biological Oxygen Demand (BOD) and water pollution as well as the expenditure of production were decreased.     

Synthesis and Spectroscopic Study of Some New Phosphoramidates,Crystal Structures of N‐Benzoyl‐N′,N″‐bis(azetidinyl)phosphoric Triamide and N‐Benzoyl‐N′,N″‐bis(hexamethylenyl)phosphoric Triamide

Some new N‐carbonyl, phosphoramidates with formula C₆H₅C(O)N(H)P(O)R₂ (R = NC₃H₆ ( 1 ), NC₆H₁₂ ( 2 ), NHCH₂CH=CH₂ ( 3 ), N(C₃H₇)₂ ( 4 )) and CCl₃C(O)N(H)P(O)R′₂ (R′ = NC₃H₆ ( 5 ), NHCH₂CH=CH₂ ( 6 )) were synthesized and characterized by ¹H, ¹³C, ³¹P NMR and IR spectroscopy and elemental analysis. The structures were determined for compounds 1 and 2 . Compound 1 exists as two crystallographically independent molecules in crystal lattice. Both compounds 1 and 2 produced dimeric aggregates via intermolecular ‐P=O…H‐N‐ hydrogen bonds, which in compound 2 is a centrosymmetric dimer. In compounds with four‐membered ring amine groups, ³J(P,C)>²J(P,C), in agreement with our previous studies about five‐membered ring amine groups. Also, ³J(P,C) values in compounds 1 and 5 are greater than in compounds with five‐, six‐ and seven‐membered ring amine groups.     

In situ vinylindole synthesis. Diels-alder reactions with maleimides to give tetrahydrocarbazoles

Tetrahydrocarbazoles have been prepared in one-flask syntheses from indoles, ketones or aldehydes, and maleimides, with acid catalysis. The reactions involve a condensation of the indole with the ketone or aldehyde, followed by an in situ trapping of the vinylindole in a Diels-Alder addition with a maleimide. Isomerization of the double bond into the indole nucleus gave the tetrahydrocarbazoles which were isolated ( 6, 9 , and 10 ). Variation of the indole, carbonyl compound, and maleimide has been explored. The predominant stereochemistry of the tetrahydro ring in the products is all-cis, although a second stereoisomer has been isolated. Two regioisomers were generated from all unsymmetrical 2-alkanones, except 2-butanone, which gave the single isomer 9a . Aromatization of tetrahydrocarbazoles 6 to carbazoles 7 was accomplished with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone.     

Two new XP(O)[NHC(CH3)3]2 phosphoramidates,with X = (CH3)2N and [(CH3)3CNH]2P(O)(O)

In N,N′‐di‐tert‐butyl‐N′′,N′′‐dimethylphosphoric triamide, C₁₀H₂₆N₃OP, (I), and N,N′,N′′,N′′′‐tetra‐tert‐butoxybis(phosphonic diamide), C₁₆H₄₀N₄O₃P₂, (II), the extended structures are mediated by P(O)...(H—N)₂ interactions. The asymmetric unit of (I) consists of six independent molecules which aggregate through P(O)...(H—N)₂ hydrogen bonds, giving R₂¹(6) loops and forming two independent chains parallel to the a axis. Of the 12 independent tert‐butyl groups, five are disordered over two different positions with occupancies ranging from to . In the structure of (II), the asymmetric unit contains one molecule. P(O)...(H—N)₂ hydrogen bonds give S(6) and R₂²(8) rings, and the molecules form extended chains parallel to the c axis. The structures of (I) and (II), along with similar structures having (N)P(O)(NH)₂ and (NH)₂P(O)(O)P(O)(NH)₂ skeletons extracted from the Cambridge Structural Database, are used to compare hydrogen‐bond patterns in these families of phosphoramidates. The strengths of P(O)[...H—N]_x (x = 1, 2 or 3) hydrogen bonds are also analysed, using these compounds and previously reported structures with (N)₂P(O)(NH) and P(O)(NH)₃ fragments.     

Accurate and approximate integrations of Drucker–Prager plasticity with linear isotropic and kinematic hardening

Up to now, some explicit approximate integration schemes based on exponential maps, for non-hardening material obeying Drucker–Prager’s criterion, have been presented. Two new exponential-based approximate formulations, for associative Drucker–Prager plasticity are developed in this article. Both are consistent and explicit algorithms. The linear isotropic and Prager’s kinematic hardening behavior are assumed. Furthermore, an accurate solution for the constitutive equations is derived. The accuracies of the suggested approximate algorithms are assessed by creating related iso-error maps. In addition, by using piecewise strain load histories, and calculating computation times, the robustness and efficiency of the formulations are demonstrated.     

Mixed finite difference and Galerkin methods for solving Burgers equations using interpolating scaling functions

The current paper proposes a technique for the numerical solution of Burgers equations. The method is based on finite difference formula combined with the Galerkin method, which uses the interpolating scaling functions. Several test problems are given, and the numerical results are reported to show the accuracy and efficiency of the new algorithm. Copyright © 2013 John Wiley & Sons, Ltd.     

Selenium heterocycles. XXXV . Synthesis and pyrrolysis of aryloxy-, arylthio-, and arylseleno-1,2,3-selenadiazoles

A series of 4-substituted-5-arylthio-1,2,3-selenadiazoles, 4-substituted-5-arylseleno-1,2,3-selenadiazoles and 4-aryloxymethyl-1,2,3-selenadiazoles were synthesized. Pyrrolysis of these compounds afforded the corresponding acetylenes XI, XIII (X = S, Se) and XII, respectively. Oxidation of 4-substituted-5-arylthio-1,2,3-selenadiazoles (XIV) with m-chloroperbenzoic acid gave 4-substituted-5-arylsulfinyl-1,2,3-selenadiazoles (XV) and 4-substituted-5-arylsulfonyl-1,2,3-selenadiazoles (XVI).     

Constitutive relations for the interaction force in multicomponent particulate flows

In the mechanics of multiphase (or multicomponent) mixtures, one of the outstanding issues is the formulation of constitutive relations for the interaction force. In this paper, we give a brief review of the various relations proposed for this interaction force. The review is tilted toward presenting the works of those who have used the mixture theory (or the theory of interacting continua) to derive or to propose a relationship for the interaction (or diffusive) force. We propose a constitutive relation which is general and frame-indifferent and thus suitable for use in many flow conditions. At the end, we provide an alternative approach for finding the drag force on a particle in a particulate mixture. This approach has been used in the non-Newtonian fluid mechanics to find the drag force on surfaces.