Validated HPLC method for determination of carboxylic acid metabolite of clopidogrel in human plasma and its application to a pharmacokinetic study

A new, simple, and reproducible method for determination of carboxylic acid metabolite of clopidogrel in human plasma has been developed. After liquid-liquid extraction in acidic medium with chloroform, samples were quantified on a Nova-pak C(8), 5 microm column using a mixture of 30 mM K(2)HPO(4)-THF-acetonitrile (pH = 3, 79:2:19, v/v/v) as mobile phase with UV detection at 220 nm. The flow rate was set at 0.9 mL/min. Ticlopidine was used as internal standard and the total run time of analysis was about 12 min. The method was linear over the range of 0.2-10 microg/mL of clopidogrel metabolite in plasma (r(2) > 0.999). The within-day and between-day precision values were in the range 1.0-4.8%. The limit of quantification of the method was 0.2 microg/mL. The method was successfully used to study the pharmacokinetics of clopidogrel in healthy volunteers.     

Simultaneous study of cure kinetics and rheology of montmorillonite/vinyl ester resin nanocomposites

In this work, the effect of quaternary ammonium salt containing nanoclay content (1–5 wt%) on phase morphology, rheology, cure kinetics, and mechanical properties of the vinyl ester resin (VER)‐based nanocomposites was studied. The morphological characterization including d‐spacing measurement, microscopy observation and phase‐height image processing were performed on the prepared nanocomposites using small angel X‐ray scattering (SAXS), transmission electron microscopy (TEM) and atomic force microscopy (AFM). According to the results obtained from these techniques, it was concluded that an intercalated morphology existed for all the nanocomposites. The kinetic analyses of the isothermal curing followed by storage modulus obtained from the rheometry experiments are shown to be an affective rheological characteristic to investigate the cure behavior of VER/clay nanocomposites. In addition, the most important finding regarding the effect of nanoclay on the cross‐linking behavior of VER systems lays on the chemisorption and physisorption of the reacting monomers and initiator molecules on the nanoclay platelets surface which is found to be responsible for the retardation of the cure reaction caused by organoclay. Eventually, the mechanical characterizations were performed through the tensile, flexural and impact analysis tests. In this case, a considerable improvement of the bulk mechanical responses such as tensile and flexural strengths and also the corresponding moduli were observed for the nanocomposites. Copyright © 2011 John Wiley & Sons, Ltd.     

The operator dose assessment of landmine detection systems using the neutron backscattering method

Personal safety issue is one of the major limitations in landmine detection by nuclear techniques. In this paper, the dose rate received by the operator of different hand-held landmine detection systems using the neutron backscattering method was investigated. Monte Carlo method was used to simulate a computational model of the body, instruments with different shielding configurations and soil with various moisture contents. The effective dose received by the different organs of the operator has been estimated by using two different approximation methods including average equivalent dose and dose equivalent assessment. The results obtained by these two methods were compared. The common results showed that the operator dose rate depends on the facility shielding, soil moisture level, and source-to-operator distance. Also, although the absorbed dose received by most organs generally decreases as a function of source to operator distance, for some organs such as kidneys and lungs it firstly increases when source-to-operator distance increases up to 0.7–1.2 m and after that the absorbed dose decreases. Furthermore, the results showed that the effective dose received by the operator has its maximum value when the source to operator distance is 0.60 m.     

SYNTHESIS OF METAL- AND PENTEL-CONTAINING HETEROCYCLES USING NITRILES AND ISONITRILES

The reaction of benzylnitrile with InMe ₃ in a molar ratio of 3:1 leads to 2-amino-N-[Me ₂ In(TMEDA)]-4-amino-3,5-diphenyl-6-benzyl-pyridine 2. CsF accelerates the reaction. The treatment of Ph ₂ CHCN with InMe ₃ in the presence of CsF gives the metalated ketenimine [(THF)Me ₂ InNCCPh ₂ ] ₂ 3. 3 and the corresponding Ga compound also can be obtained by the metathesis reaction of Me ₂ MCl with LiNu═C═CPh ₂ . The attack of the Lewis bases ^t BuELi ₂ (E = P, As) on nitriles and isonitriles also leads to oligomerizations. ^t BuAsLi ₂ reacts with two molecules of PhCN to the aromatic heterocycle [AsNC(Ph)NC(Ph)]^? by forming the salt [Li(diglyme) ₂ ] [(TMEDA)Li([AsNC(Ph)NC(Ph)]) ₂ ] 4, while the reaction of ^t BuAsLi ₂ with three equivalents of ^c HexNC leads to the dilithium compound [{Li ₂ (diglyme)} ₂ { ^t BuAs(CN ^c Hex) ₃ } ₂ ] 5. Six molecules ^c HexNC were consumed when Li ₂ P ^t Bu was added to the isonitrile to give [{Li(DME)} ₂ { ^t BuP(CN ^c Hex) ₅ (CH)}] 6.     

HPLC analysis of orlistat and its application to drug quality control studies

In this study, a high performance liquid chromatography method with UV detection was developed for determination of orlistat. The chromatographic system consisted of a Nova-Pack C18 column, an isocratic mobile phase of phosphoric acid 0.1%-acetonitrile (10 : 90, v/v) and UV detection at 205 nm. Orlistat was eluted at about 6 min with no interfering peak from excipients used for preparation of dosage form. The method was linear over the range of 10-160 microg/ml orlistat (r2 > 0.9999). The within-day and between-day precision values were also in the range of 0.10-0.59%. The appropriate dissolution conditions were also determined and applied to evaluate the dissolution profile of orlistat capsules. Optimal conditions were 1000 ml of 3% SLS in water as dissolution medium and paddle at 100 rotation per minute. The proposed method was applied successfully to the determination of orlistat content in capsules and in vitro dissolution studies.     

Superparamagnetic Fe3O4@SiO2 core–shell composite nanoparticles for the mixed hemimicelle solid‐phase extraction of benzodiazepines from hair and wastewater samples before high‐performance liquid chromatography analysis

Magnetic Fe₃O₄/SiO₂ composite core–shell nanoparticles were synthesized, characterized, and applied for the surfactant‐assisted solid‐phase extraction of five benzodiazepines diazepam, oxazepam, clonazepam, alprazolam, and midazolam, from human hair and wastewater samples before high‐performance liquid chromatography with diode array detection. The nanocomposite was synthesized in two steps. First, Fe₃O₄ nanoparticles were prepared by the chemical co‐precipitation method of Fe(III) and Fe(II) as reaction substrates and NH₃/H₂O as precipitant. Second, the surface of Fe₃O₄ nanoparticles was modified with shell silica by Stober method using tetraethylorthosilicate. The Fe₃O₄/SiO₂ composite were characterized by X‐ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, and vibrating sample magnetometry. To enhance their adsorptive tendency toward benzodiazepines, cetyltrimethylammonium bromide was added, which was adsorbed on the surface of the Fe₃O₄/SiO₂ nanoparticles and formed mixed hemimicelles. The main parameters affecting the efficiency of the method were thoroughly investigated. Under optimum conditions, the calibration curves were linear in the range of 0.10–15 μgmL^?1. The relative standard deviations ranged from 2.73 to 7.07%. The correlation coefficients varied from 0.9930 to 0.9996.     

Design a robust sliding mode controller based on the state and parameter estimation for the nonlinear epidemiological model of Covid-19

In this research, the challenging problem of Covid-19 mitigation is looked at from an engineering point of view. At first, the behavior of coronavirus in the Iranian and Russian societies is expressed by a set of ordinary differential equations. In the proposed model, the control input signals are vaccination, social distance and facial masks, and medical treatment. The unknown parameters of the system are estimated by long short-term memory (LSTM) algorithm. In the LSTM algorithm, the problem of long-term dependency is prevented. The uncertainty and measurement noises are inherent characteristics of epidemiological models. For this reason, an extended Kalman filter (EKF) is developed to estimate the state variables of the proposed model. In continuation, a robust sliding mode controller is designed to control the spread of coronavirus under vaccination, social distance and facial masks, and medical treatment. The stability of the closed-loop system is guaranteed by the Lyapunov theorems. The official confirmed data provided by the Iranian and Russian ministries of health are employed to simulate the proposed algorithms. It is understood from simulation results that global vaccination has the potential to create herd immunity in long term. Under the proposed controller, daily Covid-19 infections and deaths become less than 500 and 10 people, respectively.

     

Phosphotungstic acid grafted zeolite imidazolate framework as an effective heterogeneous nanocatalyst for the one‐pot solvent‐free synthesis of 3,4‐dihydropyrimidinones

Phosphotungstic acid (H₃PW₁₂O₄₀, PTA) supported on ZIF‐9(NH₂) was synthesized for the first time and performed as an effective and environmental friendly catalyst in the one‐pot three component Biginelli condensation of different substituted benzaldehydes with ethyl acetoacetate and urea to afford the corresponding 3,4‐dihydropyrimidin‐2‐(1H)‐ones under solvent‐free conditions. ZIF‐9(NH₂) and the prepared nanocatalyst PTA@ZIF‐9(NH₂) were characterized by XRD, FESEM, TEM, EDX, BET, AAS, TGA, UV–Vis, and FT‐IR. After reaction, the nanocatalyst can be easily separated from the reaction mixture by centrifuge and the recovered catalyst can be reused for at least five times with a 14% reduction in yield after the fifth run. This study showed that ZIF‐9(NH₂) can be utilized as a promising support for PTA and developed a highly active, stable and reusable heterogeneous catalyst under easy reaction condition in the multi‐component organic synthesis.     

Equisetum arvense As an abundant source of silica nanoparticles. SiO2/H3PW12O40 nanohybrid material as an efficient and environmental benign catalyst in the synthesis of 2‐amino‐4H‐chromenes under solvent‐free conditions

Uniform SiO₂ nanoparticles were successfully prepared from Equisetum arvense obtained from the north‐east of Iran. Then, surface modification of the extracted nanoparticles was performed with a methanol solution of H₃PW₁₂O₄₀ via wet impregnation method. The prepared nanocatalyst was characterized by XRD, FESEM, ICP, UV–Vis, and FT‐IR spectroscopy. The supported heterogeneous nanocatalyst was successfully applied as a Lewis/Bronsted acid catalyst in the synthesis of a series of substituted 4H–chromenes via condensation of aromatic aldehydes, malononitrile, and 4‐hydroxycoumarin under solventless conditions with fine yields in appropriately short times.