Analysis of primaquine and its metabolite carboxyprimaquine in biological samples: enantiomeric separation, method validation and quantification

The clinical formulation of primaquine (PQ) is a mixture of (−)‐(R)‐ and (+)‐(S)‐ primaquine enantiomers which may show different pharmacokinetic and pharmacodynamic properties. To assess the efficacy and toxicity of primaquine enantiomers, a method using LC‐MSD‐TOF has been developed. The enantiomers were well separated using a Chiralcel OD column (250 × 4.6 mm, 10 µm) with a linear gradient of mobile phase consisting of acetonitrile (0.1% formic acid) and aqueous ammonium formate (20 mm ; 0.1% formic acid) adjusted to pH 5.9 at a flow rate of 0.7 mL/min. The method was validated for linearity, precision, accuracy and limits of detection and quantification. The calibration curves were linear with all correlation coefficients being >0.999. The average recoveries of (−)‐(R)‐ and (+)‐(S)‐primaquine and (−)‐(R)‐ and (+)‐(S)‐carboxyprimaquine were 88 and 92%, respectively, in spiked human plasma and 89 and 93% respectively in spiked mouse plasma samples. The RSD of (−)‐(R)‐ and (+)‐(S)‐primaquine and (−)‐(R)‐ and (+)‐(S)‐carboxyprimaquine were 2.15, 1.74, 1.73 and 2.31, respectively, in spiked human plasma and 2.21, 1.09, 1.95 and 1.17% in spiked mouse plasma, respectively. The intra‐day and inter‐day precisions expressed as RSD were lower than 10% in all analyzed quality control levels. The method as reported is suitable for study of the pharmacokinetic and pharmacodynamic properties of the enantiomers of primaquine. The method was successfully applied to study plasma pharmacokinetic profile of enantiomers of primaquine and carboxyprimaquine in mice administered with primaquine in racemic form. The analytical method was found to be linear, accurate, precise and specific. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis of Dihydropyridine Derivatives under Eco‐friendly Approach and Investigation of Cytotoxic Activity

In an effort for development of innovative biologically active agents, a sequence of 1,4‐dihydropyridine analogues was synthesized through the green synthetic method. In addition, all compounds were evaluated for their cytotoxic activities against three human cancer cell lines and mouse melanoma and figured out the most active compounds. Besides, promoter reusability, easy handling of the chemical reagent, simple reaction process, time minimization, ethanol–water solvent compatibility, and cost reduction reagent are key tools for this fruitful path. Thus, these examinations recommended that dihydropyridine and their derivatives are motivating moieties for the discovery of new anticancer drugs.     

An effective green and ecofriendly catalyst for synthesis of bis(indolyl)methanes as promising antimicrobial agents

An effective and suitable meglumine‐catalyzed high‐yielding process was considered and engaged for the synthesis of new bis(indolyl)methanes at ambient temperature under aqueous conditions. The catalytic reaction proceeds very smoothly. Clean reaction, ease of product isolation/purification, easily available reactant and ecofriendly reaction conditions are the notable advantages of the present methodology. All the title compounds were characterized by IR, 1H, ¹³C NMR, and mass spectra. All the synthesized compounds were tested for antimicrobial activity, and the results indicated that most of the synthesized compounds exhibited excellent activity against the tested microorganisms. In this new series, compound 3l , having nitro substituent on the aromatic ring, showed exceptional potent inhibitory activity against Pseudomonas aeruginosa and Penicillium chrysogenum.     

An Experimental Approach to Correcting Counting Errors in the Aerodynamic Particle Sizer (APS Model 3310)

This paper describes the different ways of analyzing the output of a real-time device for measuring and counting airborne particles, the aerodynamic particle sizer (APS). This instrument is very widely used in aerosol research throughout the world. It is a time-of-flight instrument in which a particle's measured transit time in the changing flow in a jet passing between two laser beams is converted to its aerodynamic diameter. As the particle passes between the two laser beams, two signal processors, the small particle processor (SPP) and the large particle processor (LPP), independently provide measures of the particle's transit time from the light pulses that are produced. This information is related to the aerodynamic particle diameter of the particle (d_ae) by means of calibration against ‘unit’ density (1000 kg/m³) spheres. If more than one particle is involved in the analysis of particle transit time, then it gives rise to coincidence effects, resulting in ‘phantom’ particle generation. The SPP is known to generate phantom counts, while the LPP is known to reduce phantom counts. A new method is described in this paper that gives guidance on how to deal with such coincidence problems. The principle is that it relies on additional information to obtain ‘correction factors’. In this case, well-established theory for the aspiration efficiencies of thin-walled aerosol sampling probes has been used along with corresponding experimental data obtained in a wind tunnel using the APS. Results using this method are compared with various other methods that have been tried in the past. The paper provides insights on to how the user can operate the APS to avoid counting errors like those described, and the advantages and limitations of different correction methods are discussed.     

Chemical fingerprinting of valeriana species: simultaneous determination of valerenic acids, flavonoids, and phenylpropanoids using liquid chromatography with ultraviolet detection

The roots and rhizomes of various valeriana species are currently used as a sleeping aid or mild sedative. A liquid chromatography method has been developed that permits the analysis of chlorogenic acid, lignans, flavonoids, valerenic acids, and valpotrates in various valerian samples. The best results were obtained with a Phenomenex Luna C18(2) column using gradient elution with a mobile phase consisting of water and 0.05% phosphoric acid and 2-100% acetonitrile-methanol (1 + 1) with 0.05% phosphoric acid. The flow rate was 0.8 mL/min and ultraviolet detection was at 207, 225, 254, 280, and 325 nm. Different valerian species and commercial products showed remarkable quantitative variations. Chlorogenic acid (0.2-1.2%), 3 lignans, linarin (0.002-0.24%), and valepotriates were detected in all the valeriana species analyzed. Highest amounts of valerenic acids were detected in V. officinalis L., trace amounts in V. sitchensis, and none in the other species analyzed.     

HPTLC Method for Determination of 20-Hydroxyecdysone in Sida rhombifolia L. and Dietary Supplements

Naturally occurring 20-hydroxyecdysone is an important anabolic ecdysteroid. A simple thin-layer chromatography method to quantitate 20-hydroxyecdysone in methanolic extract of the whole plant material of Sida rhombifolia L. was developed. This method was successfully applied for quantitative evaluation of dietary supplements. The separation was achieved on glass TLC plates coated with silica gel 60F254, using chloroform: methanol (8:2 v/v) as developing solvent. Densitometric evaluation of 20-hydroxyecdysone was performed at 250 nm in reflectance/absorbance mode. The calibration was in the range of 200–1,000 ng spot^?1 and correlation coefficient for the calibration curve was >0.999. In addition, for six different Sida species unique fingerprints were obtained on the HPTLC plate.     

Design and Synthesis of Some New Benzimidazole Containing Pyrazoles and Pyrazolyl Thiazoles as Potential Antimicrobial Agents

A new class of bis heterocycles‐benzimidazolyl pyrazoles were prepared from the Michael acceptor (E)‐3‐(1H‐benzimidazol‐2‐yl)‐1‐aryl‐prop‐2‐en‐1‐one. The thiamide group was exploited to develop thiazole ring on treatment with p‐fluorophenacyl bromide to get tris heterocycles. All the lead compounds were tested for antimicrobial activity. The compound 7d having nitro substituent on the aromatic ring showed greater antimicrobial activity particularly against Pseudomonas aeruginosa and Penicillium chrysogenum.     

Rapid analysis of lignans from leaves of Podophyllum peltatum L. samples using UPLC‐UV‐MS

A new rapid UPLC‐UV‐MS method has been developed that permits the analysis of four lignans (4′‐O‐demethylpodophyllotoxin, podophyllotoxin, α‐peltatin and β‐peltatin) in P. peltatum L. Podophyllotoxin is a natural lignan that is being used as a precursor for the semi‐synthetic anti‐cancer drugs etoposide, teniposide and etopophos. The chromatographic separation was achieved using a reversed‐phase C₁₈ column with a mobile phase of water and acetonitrile, both containing 0.05% formic acid. Analyses of P. peltatum leaves collected from different colonies within a single site indicated a significant variation in 4′‐O‐demethylpodophyllotoxin, α‐peltatin, podophyllotoxin and β‐peltatin content. Within 3.0 min four main lignans could be separated with detection limits of 0.1, 0.3, 0.3 and 0.2 μg/mL, respectively. 4′‐O‐demethylpodophyllotoxin and α‐peltatin appeared most prominently among the lignans obtained. The podophyllotoxin content was found in the range of 0.004–0.77% from 16 samples collected from 6 colonies within the same site. The content of podophyllotoxin is directly proportional to the content of 4′‐O‐demethylpodophyllotoxin and inversely proportional to α‐peltatin and β‐peltatin content. LC‐mass spectrometry coupled with electrospray ionization (ESI) interface method is described for the identification of four lignans in various populations of plant samples. By applying principal component analysis and hierarchical cluster analysis, Podophyllum samples collected from various colonies within a location were distinguished. Copyright © 2011 John Wiley & Sons, Ltd.     

Analysis of suddenly started laminar flow in the entrance region of a circular tube

Suddenly started laminar flow in the entrance region of a circular tube, with constant inlet velocity, is investigated analytically by using integral momentum approach. A closed form solution to the integral momentum equation is obtained by the method of characteristics to determine boundary layer thickness, entrance length, velocity profile, and pressure gradient.Nomenclature M(, , ) a function - N(, , ) a function - p pressure - p* p/1/2U ², dimensionless pressure - Q(, , ) a function - R radius of the tube - r radial distance - Re 2RU/, Reynolds number - t time - U inlet velocity, constant for all time, uniform over the cross section - u velocity in the boundary layer - u* u/U, dimensionless velocity - u ₁ velocity in the inviscid core - x axial distance - y distance perpendicular to the axis of the tube - y* y/R, dimensionless distance perpendicular to the axis - boundary layer thickness - * displacement thickness - /R, dimensionless boundary layer thickness - momentum thickness - absolute viscosity of the fluid - /, kinematic viscosity of the fluid - x/(R Re), dimensionless axial distance - density of the fluid - tU/(R Re), dimensionless time - _w wall shear stress