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.     

One-pot Synthesis,Crystal Structures and Antimicrobial Activities of Two New 1,4-Disubstituted 1,2,3-Triazole-4-Carboxylates

Two new 1,4-disubstituted 1,2,3-triazoles-4-carboxylates were synthesized via click reaction. Compound 1a was synthesized by the interaction of 6-nitro-tetrazolo[1.5-a]-pyridine with ethyl propynoate at room temperature in the presence of Cu(OAc)2 as a catalyst and THF as solvent. Compound 1b was also synthesized by the same manner except that tert-butyl propionate, instead of ethyl propynoate, was used. The compounds were characterized by IR, 1H-NMR, 13C-NMR and single-crystal X-ray diffraction analysis. Compound 1a(C10H9N5O4) crystallizes in the triclinic system, space group P1 with a = 5.0894(9), b = 8.9834(13), c = 13.089(2) ?, α= 83.041(7), β= 80.256(7), γ=87.296(8)°, V = 585.24(16)?3, Z = 2, Mr = 263.22, crystal size(mm) = 0.37 × 0.20 ×0.18,(I 2σ(I)) = 8557, 2493, 1229, Rint = 0.057. Compound 1b(C12H13N5O4) crystallizes in the monoclinic system, space group P21/c with a = 6.8854(5), b = 21.783(2), c = 9.3986(8) ?,β = 93.239(4)°, V = 1407.4(2)?3, Z = 4, Mr = 291.27, crystal size(mm) = 0.38 × 0.22 × 0.20,(I 2σ(I)) = 11842, 3172, 1866, Rint = 0.047. Antimicrobial assay results showed that the title compounds display excellent activities to different bacterial and fungal strains.     

Asymptotic discrimination between renewal processes

Limit theorems for the logarithm of the likelihood ratio are proven. With their help the rate of decrease in the probability of errors of the second kind in the Neumann-Pierson criterion is established.Translated from Ukrainskii Matematicheskii Zhurnal, Vol. 44, No. 10, pp. 1382–1388, October, 1992.     

Synthesis of (1R,4R,7S)- and (1S,4S,7S)-2-(4-tolylsulfonyl)-5-phenyl-methyl-7-methyl-2,5-diazabicyclo[2.2.1]heptanes via regioselective opening of 3,4-epoxy-d-proline with lithium dimethyl cuprate

The synthesis of (1S,4S,7S)- and (1R,4R,7S)-2-(4-tolylsulfonyl>5-phenylmethyl-7-rnethyl-2,5-diazabicyclo-[2.2.1]heptanes ( 20 ) and ( 22 ) from trans 4-hydroxy-L-proline is described.     

Aminopropylcellulose,synthesis and derivatization

The preparation of 3-aminopropylcellulose from cyanoethylcellulose is readily achieved. Reduction of the cyano groups with borane-dimethyl sulfide in tetrahydrofuran or a borane-tetrahy-drofuran complex proceeds quantitatively in 3 h to a corresponding 3-aminopropylcellulose. The presence of primary amine functions is confirmed by spectroscopy and a positive ninhydrin test; the concentration of amino substituents, as ascertained by titration, ranged from 1.2 to 6.4 meq/g. Because the derivatives are neither soluble nor excessively swollen in water, applications as ion-exchange resins or chromatographic supports can be envisioned. Treatment of 3-aminopropyl-cellulose with acetyl chloride, phenyl isocyanate, or p-toluenesulfonyl isocyanate produced 3-acetamido-, 3-(N′-phenyluredo)-, or 3-(N′-p-toluenesulfonyluredo)-N-propylcellulose. Alkylation with methyl chloride yielded a water-soluble quaternary ammonium salt.     

Determining the chromophore in the amylopectin–iodine complex by theoretical and experimental studies

A partial hydrolysis of amylose followed by the addition of iodine provides a spectrum almost identical to that of the amylopectin–iodine (API) complex suggesting the involvement of smaller “amylose-like” units in the API complex. Our theoretical studies on different polyiodine and polyiodide species suggest that a nearly linear I₄ unit stabilized within the cavity of a small “amylose-like” helix is responsible for the characteristic API spectrum. Since there are 2.75 anhydroglucose residues (AGU) for every iodine atom in the amylose–iodine (AI) complex and a structural similarity exists between the API and the AI (amylose–iodine) complexes, we identify (C₆H₁₀O₅)₁₁I₄ to be the chromophore in the API complex. © 1994 John Wiley & Sons, Inc.     

Screening of urban aerosol particulate composites for selected metal distribution and their dependence on meteorological parameters

Local atmospheric aerosol particulate samples, collected as composites on daily 6-12 hour basis, at Quaid-i-Azam University campus, Islamabad, Pakistan, using high volume sampling technique, were analysed for Pb, Na, K, Fe, Mn, Cd, Cr, Ni, Zn and Co by FAAS method. The monitoring period ran from October, 2001 through March, 2002, with a total of 105 samples collected on cellulose filters, treated in part with the HNO3-based wet digestion method for metal quantification, and for particle size distribution separately. The metal content of the aerosols was examined in relation to dependence on meteorological parameters, such as temperature, relative humidity, wind speed, sun shine and pan evaporation. Statistical correlation analysis was conducted for multiple metal pairs in aerosols, and the data were examined in relation to meteorological parameters and relevant aerosol particle size fractions. The study revealed no viable strong correlation between the meteorological parameters and metal levels; in general, however, a significant positive correlation was found for temperature. A strong positive correlation was observed for PM<25 and PM2.5-10. For coarse particles (PM10-100 and PM>100), however, a negative correlation was observed. The levels of Na, K, Fe and Zn were found in the range of 1-5 microg/m3 while those for the rest of the metals in the sub microg/m3 range. Principal component analysis and cluster analysis were performed on dataset for source identification and appointment. Largest contribution (33%) was shown by the industrial emissions followed by traffic/road dust (16.7%).     

Retention, kinetics and thermodynamics profile of cadmium adsorption from iodide medium onto polyurethane foam and its separation from zinc bulk

The sorption behaviour of 2.5 × 10⁻⁵ M solution of Cd(II) on polyurethane foam (PUF) from iodide medium have been investigated. The conditions were optimized from aqueous solutions of different pH (1-10) and of acids of varied concentration (0.01-1.0 M). The maximum concentration of KI was found to be 0.24 M and equilibration time was established to be 20 min. The data successfully followed the Freundlich and Dubinin-Radushkevich (D-R) isotherms at low metal ion concentration while Langmuir isotherm followed at higher metal ion concentration. The Freundlich parameter 1/n = 0.66 ± 0.02 have been evaluated whereas D-R isotherm yields the sorption free energy E = 10.5 ± 0.1 kJ mol⁻¹ indicating ion exchange type chemisorption. The monolayer coverage (XL) constant of Langmuir isotherm was found to be 23.7 ± 0.4 mg g⁻¹. The numerical values of thermodynamics parameters enthalpy (ΔH), entropy (ΔS) and Gibbs free energy (ΔG) indicated the endothermic and spontaneous nature of sorption. The Scatchard plot analysis was tested to evaluate the binding sites of the PUF and stability constants of sorption were determined. On the basis of these parameters, the sorption mechanism was discussed. Among the foreign ions tested, Pb(II), Hg(II), cyanide and nitrite should be absent. The clean separation of Cd(II) from Zn(II) ions in the ratio 1:250, respectively, was achieved by column chromatography.     

Computer simulations of the solvation dynamics of Coumarin 153 in dimethylsulfoxide

We report molecular dynamics (MD) simulations of the solvation dynamics of Coumarin 153 in liquid dimethylsulfoxide using two distinct sets of partial charges for the coumarin probe. The excited state dipole moment of the coumarin and the dynamic Stokes shift in solution depend significantly on the type of charge distributions used. Nevertheless, the overall characteristics of the solvation responses obtained from both sets of charges are very similar and show good agreement with time-dependent Stokes shift experiments. Microscopic details of the solvent reorganization around the probe are discussed in light of the charge transfer upon photoexcitation.     

Synergic effect of triphenylphosphine oxide (TPPO) on the extraction of Hg(II), Se(IV), Co(II) and Mn(II) with fluorinated pyrazolone (HPMTFP)

Extraction of Hg(II), Se(IV), Mn(II) and Co(II) has been carried out with 1-phenyl-3-methyl-4-trifluoroacetyl-2-pyrazolin-5-one (HPMTFP) and triphenylphosphine oxide (TPPO) into chloroform from pH 1–10. Quantitative extraction of Hg(II), Mn(II) and Co(II) at pH 4 with equimolar 0.05M (PMTFP+TPPO) in chloroform was observed. Se(IV) remains unextracted at this pH range. The stoichiometric composition of the extracted complexes M(PMTFP)₂·nH₂O (M=Mn, Hg), M(PMTFP)₂·2TPPO (M=Mn and Co) and Co(PMTFP)₂·TPPO·H₂O at less than 0.1M TPPO has been established. The formation constantsK _m,0 andK _m,n and stability constants _m,n have been computed. The analytical method developed was applied to the IAEA standard reference material (SRM) potato fluor V-4 for the determination of these elements using NAA technique.