Development and validation of a sensitive LC-MS/MS method with electrospray ionization for quantitation of zafirlukast, a selective leukotriene antagonist in human plasma: application to a clinical pharmacokinetic study

A highly sensitive and specific LC-MS/MS method has been developed and validated for the estimation of zafirlukast (ZFK) with 500 microL human plasma using valdecoxib as an internal standard (IS). The API-4,000 LC-MS/MS was operated under multiple reaction-monitoring mode using the electrospray ionization technique. The assay procedure involved extraction of ZFK and IS from human plasma with ethyl acetate. The resolution of peaks was achieved with 10 mm ammonium acetate (pH 6.4):acetonitrile (20:80, v/v) on a Hypersil BDS C(18) column. The total chromatographic run time was 2.0 min and the elution of ZFK and IS occurred at approximately 1.11 and 1.58 min, respectively. The MS/MS ion transitions monitored were 574.2 --> 462.1 for ZFK and 313.3 --> 118.1 for IS. The method was proved to be accurate and precise at a linearity range of 0.15-600 ng/mL with a correlation coefficient (r) of >or=0.999. The method was rugged with 0.15 ng/mL as lower limit of quantitation. The intra- and inter-day precision and accuracy values were found to be within the assay variability limits as per the FDA guidelines. The developed assay method was applied to a pharmacokinetic study in human volunteers following oral administration of 20 mg ZFK tablet.     

Synthesis and bio‐activity of novel iminophosphoranes

The title compounds ( 5a‐j ) were synthesized by a two step process. 4‐Chlorophenyl and bis(2‐chloroethyl) amino‐dibromophosphites ( 1a and 1b ) were reacted with 1,8‐diaminonaphthalene ( 2 ) to form the diazaphosphinines ( 3a and 3b ). They were further reacted with different alkyl azides ( 4a‐e ) in THF at 50‐55 °C under N₂ atmosphere to afford the corresponding iminophosphoranes ( 5a‐j ). Their structures were established by elemental analysis, IR, ¹H, ¹³C, ³¹P NMR and Mass spectral data. All of them exhibited moderate antibacterial activity.     

AlCl3/PCC-SiO2-Promoted Oxidation of Azaindoles and Indoles

Abstract

A simple and efficient method is described for the oxidation of 7-azaindoles and indoles to 7-azaisatins and isatins using pyridinium chlorochromate–silica gel (PCC-SiO₂) with the aid of Lewis acid catalyst aluminium chloride (AlCl₃) in dichloroethane. Simplicity of the reaction conditions, easy workup procedure, and good yields are the key features of this protocol.     

Fast and safe: accelerated gradient methods with optimality certificates and underestimate sequences

Computational Optimization and Applications - In this work we introduce the concept of an Underestimate Sequence (UES), which is motivated by Nesterov’s estimate sequence. Our definition of a...     

Preconditioners for spectral element methods for elliptic and parabolic problems

In this paper we propose preconditioners for spectral element methods for elliptic and parabolic problems. These preconditioners are constructed using separation of variables and are easy to invert. Moreover they are spectrally equivalent to the quadratic forms which they are used to approximate.     

A New Abietane Diterpenoid from Plectranthus bishopianus Benth.

Chemical examination of the MeOH extract of Plectranthus bishopianus Benth ., a rare and endangered plant, resulted in isolation of a new abietane diterpene, 6β‐hydroxy‐7α‐methoxyroyleanone ( 1 ), along with two more diterpenoids, 6,7‐dehydroroyleanone, and 6β,7α‐dihydroxyroyleanone, a triterpene oleanolic acid, and two sterols, β‐sistosterol and stigmasterol. The structures of the isolated compounds were elucidated on the basis of spectroscopic data and also by comparison with authentic samples.     

Sensitive determination of propoxur by spectrophotometry using 3-aminopyridine.

A simple spectrophotometric method for the determination of propoxur, a widely used insecticide, in various environmental samples and pesticide formulations is described. The method is based on the coupling of the hydrolysis product of propoxur with diazotized 3-aminopyridine in an alkaline medium, to form an azo-dye which has a maximum absorbance at 463 nm. Beer's law is obeyed over the concentration range of 0.05 to 1.2 microg ml(-1) of propoxur. The molar absorptivity and Sandell's sensitivity are found to be 3.10 x 10(4) l mol(-1) cm(-1) and 0.007 microg cm(-2), respectively. The important analytical parameters and optimum reaction conditions were evaluated. The method is free from the interference of other commonly used pesticides and inorganic metal ions.     

New Synthesis of Simvastatin

A noninfringing synthesis of simvastatin 1, starting from lovastatin 2, is presented. This synthesis features the protection of the free hydroxyl group of the lovastatin with 3,4-dihydro-2H-pyran (DHP) and opening of the lactone ring with n-BuNH₂ to afford amide 4 as a key intermediate.     

An expedient synthesis of pyrrolidinyl spirooxindole grafted 3-nitrochromanes through 1,3-dipolar cycloaddition reaction of azomethine ylides

A facile one-pot synthesis of pyrrolidinyl-spirooxindole grafted 3-nitrochromanes has been accomplished by 1,3-dipolar cycloaddition (1,3-DC) reaction of 3-nitrochromenes with azomethine ylides generated in situ from isatin and secondary amino acids. The regio- and stereochemical outcome of the cycloaddition reaction was ascertained by X-ray crystallographic analysis.     

Syntheses and Antimicrobial Activity of Some Novel 6‐Substituted Dibenzo[d,f][1,3,2]dioxaphophepin‐6‐oxides,Sulfides, and Selenides

6‐Substituted‐dibenzo[d, f][1,3,2]dioxaposphepin‐6‐oxides, sulfides, and selenides (5a–i, 6a–d, and 7a–d) were synthesized by reacting 2,2′‐biphenol (1) with phosphorus tribromide in the presence of triethylamine at 0–30°C and subsequent reaction of the monobromide (2) with different Grignard reagents (3) at room temperature. The products (4) were converted to corresponding oxides, sulfides, and selenides (5a–i, 6a–d, and 7a–d) by oxidation with H₂O₂ at room temperature and refluxing with sulfur and selenium respectively. The chemical structures of all the products were confirmed by analytical, IR, NMR (¹H, ¹³C, and ³¹P), and mass spectral data. Most of these compounds exhibited moderate antimicrobial activity.