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.     

Rapid and efficient synthesis of optically active pyrazoles under solvent-free conditions

2-Formyl glycals undergo rapid condensation with arylhydrazines under solvent-free conditions to give the corresponding optically pure 4-substituted pyrazoles in good yields with high selectivity. The stereochemistry of the products was assigned by various NMR experiments.     

Vanadium(III) chloride catalyzed Biginelli condensation: solution phase library generation of dihydropyrimidin-(2H)-ones

The three component condensation of an aldehyde, a β-keto ester and urea (thiourea) in the presence of a catalytic amount of VCl₃ is disclosed for the solution phase synthesis of dihydropyrimidinones. The ease of synthesis and work-up allowed the parallel synthesis of a 48-membered library of dihydropyrimidinones quickly and efficiently in good yields.     

Friedel-Crafts alkylation of indoles with epoxides catalyzed by nanocrystalline titanium(IV) oxide

Friedel-Crafts alkylation of indoles with epoxides to afford 3-alkyl indole derivatives at room temperature with moderate to good yields and high regioselectivity using nanocrystalline titanium(IV) oxide catalyst is described.     

Study of solar features causing GMSs with 250γ<<Emphasis Type="Italic">H</Emphasis><400γ

The effect of solar features on geospheric conditions leading to geomagnetic storms (GMSs) with planetary index,A ^P ≥ 20 and the range of horizontal component of the Earth’s magnetic fieldH such that 250γ <H < 400γ has been investigated using interplanetary magnetic field (IMF), solar wind plasma (SWP) and solar geophysical data (SGD) during the period 1978–99. Statistically, it is observed that maximum number of GMSs have occurred during the maximum solar activity years of 21st and 22nd solar cycles. A peculiar result has been observed during the years 1982, 1994 when sunspot numbers (SSNs) decrease very rapidly while numbers of GMSs increase. No distinct association between yearly occurrence of disturbed days and SSNs is observed. Maximum number of disturbed days have occurred during spring and rainy seasons showing a seasonal variation of disturbed days. No significant correlation between magnitude (intensity) of GMSs and importance ofH _α , X-ray solar flares has been observed. Maximum number of GMSs is associated with solar flares of lower importance, i.e., SF during the period 1978-93.H _α , X-ray solar flares occurred within lower helio-latitudes, i.e., (0–30)°N to (0–30)°S are associated with GMSs. NoH _α , X-ray solar flares have occurred beyond 40°N or 40°S in association with GMSs. In helio-latitude range (10–40)°N to (10–40)°S, the 89.5% concentration of active prominences and disappearing filaments (APDFs) are associated with GMSs. Maximum number of GMSs are associated with solar flares. Coronal mass ejections (CMEs) are related with eruptive prominences, solar flares, type IV radio burst and they occur at low helio-latitude. It is observed that CMEs related GMS events are not always associated with high speed solar wind streams (HSSWSs). In many individual events, the travel time between the explosion on the Sun and maximum activity lies between 58 and 118 h causing GMSs at the Earth.     

Optimization of the process variables for the synthesis of cardanol-based novolac-type phenolic resin using response surface methodology

Models capable of predicting the maximum extent of conversion (p) of cardanol-based novolac-type phenolic resin, have been developed using response surface methodology to determine the optimum reaction conditions. Three-dimensional response surface and their contour plot were drawn. The maximum extent of conversion (98.93%) was predicted when the cardanol was condensed with formaldehyde (molar ratio 1:0.652) at 119.84 °C for a time period of 3 h with the catalyst (e.g., citric acid) concentration of 1.988% of total volume of cardanol and formaldehyde. The pH of the reaction mixture was maintained at 3.0. These predicted values for optimum process conditions were in good agreement with experimental data.     

Binding studies of sodium dodecyl benzene sulphonate with poly(N-vinyl-2-pyrrolidone)

The binding of sodium dodecyl benzene sulphonate (SDBS) with poly(N-vinyl-2-pyrrolidone) (PVP) has been investigated at 303.15 and 313.15 K using equilibrium dialysis, surface tension, viscosity, ultrasound velocity and ultrasound absorption techniques. From each of these studies four distinct regions of SDBS-PVP interactions were observed. Interaction of SDBS with PVP was found to involve the binding of surfactant dimers with the polymer molecule followed by usual micellization. The binding data has been analyzed in terms of various models of polymer-surfactant interaction.     

Studies on the interaction of Eu(III) with lawsone (2-hydroxy-1,4-naphthoquinone), lapachol (2-hydroxy-3-(3-methyl-2-butenyl)-1,4-naphthoquinone), juglone (5-hydroxy-1,4-naphthoquinone) and plumbagin (2-methyl-5-hydroxy-1,4-naphthoquinone)

pH-metric studies show that one mole of Eu(III) interacts with three molecules of each of juglone, plumbagin, lawsone and lapachol in solution. The stability and thermodynamics of these systems (50% aqueous acetone, 0.1 M KNO₃ ionic strength) are discussed and explained.     

Synthesis and structural characterisation of a novel tris-methylene bridged compound (NO) 4Fe2 Se(μ-CH2)3

The tris-methylene bridged compound (NO)₄Fe₂Se(μ-CH₂)₃ has been isolated. It has been characterised by IR and ¹H, ¹³C, and ⁷⁷Se NMR spectroscopy. Its structure has been determined by single-crystal X-ray diffraction methods. The structure consists of a heavy atom triangle consisting of one Se and two Fe atoms. The Fe-Fe and the two Fe-Se edges are bridged by methylene groups.