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.     

On General Mixed Quasivariational Inequalities

In this paper, we suggest and analyze several iterative methods for solving general mixed quasivariational inequalities by using the technique of updating the solution and the auxiliary principle. It is shown that the convergence of these methods requires either the pseudomonotonicity or the partially relaxed strong monotonicity of the operator. Proofs of convergence is very simple. Our new methods differ from the existing methods for solving various classes of variational inequalities and related optimization problems. Various special cases are also discussed.     

Parametric Quintic-Spline Approach to the Solution of a System of Fourth-Order Boundary-Value Problems

In this paper, we use parametric quintic splines to derive some consistency relations which are then used to develop a numerical method for computing the solution of a system of fourth-order boundary-value problems associated with obstacle, unilateral, and contact problems. It is known that a class of variational inequalities related to contact problems in elastostatics can be characterized by a sequence of variational inequations, which are solved using some numerical method. Numerical evidence is presented to show the applicability and superiority of the new method over other collocation, finite difference, and spline methods.     

Some algorithms for hemiequilibrium problems

In this paper, we suggest and analyze a class of iterative methods for solving hemiequilibrium problems using the auxiliary principle technique. We prove that the convergence of these new methods either requires partially relaxed strongly monotonicity or pseudomonotonicity, which is a weaker condition than monotonicity. Results obtained in this paper include several new and known results as special cases.     

Modified Householder iterative method free from second derivatives for nonlinear equations

In this paper, we suggest and analyze a new two-step predictor–corrector type iterative method free from second derivatives for solving nonlinear equations of the type f(x)=0. This new method includes the two-step Newton method as a special case. We prove that the new iterative method is of fourth-order. Several examples are given to illustrate the efficiency of this new method and its comparison with other iterative methods. This method can be considered as a significant improvement of the Newton method and its variant forms.     

Iterative Schemes for Nonconvex Variational Inequalities

In this paper, we suggest and analyze some iterative methods for solving nonconvex variational inequalities using the auxiliary principle technique, the convergence of which requires either only pseudomonotonicity or partially relaxed strong monotonicity. Our proofs of convergence are very simple. As special cases, we obtain earlier results for solving general variational inequalities involving convex sets.     

Selected valence electron split-shell molecular orbital calculations on the diatomic interhalogen molecules

Selected valence electron split-shell molecular orbital calculations have been performed on the diatomic interhalogen molecules in order to obtain their binding energies, equilibrium internuclear distances, vibrational force constants, dipole moments and nuclear quadrupole coupling constants. The results are compared with the corresponding closedshell values and with those of some previous semiempirical and nonempirical all valence electron calculations. It is observed that the selected valence electron split-shell molecular orbital method which involves the least amount of computations yields results in better agreement with experiment than other methods.     

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.