Validation of LC/MS electrospray ionisation method for the estimation of ursodiol in human plasma and its application in bioequivalence study

A novel High Performance Liquid Chromatography-electrospray mass spectrometric method has been developed for the estimation of Ursodiol (Ursodeoxycholic acid)--a bile acid, in human plasma using Ornidazole as internal standard. The methodology involved solid phase extraction of the analyte from human plasma matrix. The chromatographic separation was achieved within seven minutes by an isocratic mobile phase containing 1.0 mM ammonium acetate and Acetonitrile (65:35, v/v), flowing through XTerra MS C18, 100 x 2.1, 3.5 microm analytical column, at a flow rate of 0.2 ml/min. Ion signals were measured in negative mode for Ursodiol and internal standard at m/z 391.3 and 278.1, respectively. A detailed validation of the method was performed as per USFDA guidelines and the standard curves were found to be linear in the range 50.0 ng/ml to 3000.0 ng/ml with the mean correlation coefficient more than 0.99. The absolute recovery was more than 54.90% for Ursodiol and 76.51% for internal standard. Ursodiol was stable for sixty-nine days at -70 degrees C and for eight hours at ambient temperature. After extraction from plasma, the reconstituted samples of Ursodiol were stable in autosampler at 10 degrees C for forty-eight hours. Upon subjecting to three freeze thaw cycles, there was no change in the recovery of the analyte. The integrity of the plasma samples remained unaffected even upon four-fold dilution with drug free human plasma. The method was simple, specific, sensitive, precise, accurate and suitable for bioequivalence and pharmacokinetic studies. It was successfully applied to the pilot bioequivalence study of Ursodiol in male human subjects.     

Study of EPR, optical properties and electrical conductivity of vanadyl doped Bi2O3.PbO.B2O3 glasses

Heavy metal based oxide glasses having composition xBi(2)O(3).(0.30 - x)PbO.0.70B(2)O(3) have been prepared (0.00 < or = x < or = 0.15, mol%) containing 2.0mol% of V(2)O(5) by normal melt-quenching technique. Electron paramagnetic resonance (EPR), optical spectra and dc conductivity of these glasses have been studied. Spin Hamiltonian parameters (SHP) of VO(2+) ions, dipolar hyperfine parameter, P and Fermi contact interaction parameter, K, molecular orbital coefficients (alpha(2) and gamma(2)) and optical band gap have been calculated. It is observed that in these glasses, the tetragonal nature of V(4+)O(6) complex increases with Bi(2)O(3) content. Increase in Bi(2)O(3):PbO ratio results in the contraction of 3d(xy) orbit of the unpaired electron in the vanadium ion, and the SHP are dependent on the theoretical optical basicity, Lambda(th). In present glasses, the conductivity (activation energy) first decreases (increases) with increase in mol% of Bi(2)O(3) content upto x = 0.08 and then shows a maxima (minima) at x = 0.10 and then starts decreasing (increasing) upto x < or = 0.15 with mol% of Bi(2)O(3) content.     

Mechanism and kinetics of thermal decomposition of precipitates of the zinc oxide-aluminium oxide system from non-isothermal tg curves

Kinetics of decomposition of the precipitates of the ZnO&2sbndAl₂O₃ system, prepared by coprecipitation and mechanical mixing of the individual precipitates, have been studied. The decomposition of zinc basic carbonate is a first order rate process with an activation energy of 34.5 kcal/mole (Coats and Redfern equation). The decomposition of aluminium hydroxide is also best described as a first order rate process with one break in the Coats and Redfern plot corresponding to activation energies of 29.4 and 8.3 kcal/mole respectively. The entire course of decomposition of coprecipitated as well as mechanically mixed samples cannot be described by any one of the many rate equations available. Consequently, the Coats and Redfern equation has been employed. The plots indicate one or two breaks and thus two to three values of activation energy are reported. From the results it is to be concluded that decomposition of these precipitates is a heterogeneous process. The first step is definitely the decomposition of zinc basic carbonate followed by decomposition of aluminium hydroxide and/or interaction of the two precipitates resulting in the formation of “precursor” to spinel. The results of our earlier investigation on the same system (especially the formation of precursors) are well supported by the results reported in this investigation. p]A new equation (a modified form of the Elovich equation) has been proposed for such heterogeneous decomposition processes. The proposed equation also appears to be the general form of the equations where diffusion is the rate controlling process.     

Rapid shear viscosity calculation by momentum impulse relaxation molecular dynamics

Recently, Arya et al. [J. Chem. Phys. 113, 2079 (2000)] introduced a new molecular dynamics method to rapidly compute the viscosity of fluids. The technique, termed momentum impulse relaxation (MIR), involves the imposition of a Gaussian velocity profile on an equilibrated system, after which the decay in the profile is monitored as a function of time. The shear viscosity is computed by matching the rate of decay of the velocity profile to the corresponding solution of the Navier-Stokes equation. The method was originally applied to simple systems (argon and n-butane) and found to give a comparable accuracy to conventional equilibrium and nonequilibrium methods with more than an order of magnitude reduction in computing time. In this work, we extend and generalize the method to examine larger molecules with higher viscosities than have been examined previously. A detailed analysis of the method is given, including the effect the velocity boundary conditions have on the viscosity, the sensitivity of the results to the velocity profile fitting procedure, the effect of preequilibration of the Gaussian profile, and the effect the system size and box shape have on the accuracy and speed of the method. It is shown that the MIR method can be extended to treat multiatom systems without loss of accuracy or computational efficiency.     

Interaction of chloroform with aniline, o-toluidine and N,N-dimethyl aniline

Heats of mixing aniline, o-toluidine, and N,N-dimethyl aniline with chloroform have been determined by an adiabatic calorimeter. The results have been examined for molecular interactions between them, and they indicate that aniline and o-toluidine are associated through hydrogen bonds. Enthalpy of bond formation in a 1:1 complex has also been determined.     

Efficient oxidizing methods for the synthesis of oxandrolone intermediates

Mild, efficient and eco-friendly oxidation of 17alpha-methylandrostan-3beta-17beta-diol (1) has been studied with three different reagents viz. pentavalent iodine reagent 2-iodoxy benzoic acid (IBX) in DMSO at 65 degrees C, sodium hypochlorite and H2O2/Na2WO4 under phase transfer conditions to give 17beta-hydroxy-17alpha-methylandrostan-3-one (mestanolone 2), a drug intermediate as oxidized product. The H2O2/Na2WO4/PTC gave mestanolone in high yield and purity whereas sodium hypochlorite/PTC system yielded some chlorinated material along with the mestanolone. However, 1 with 2.5 equivalent of IBX gave 17beta-hydroxy-17alpha-methyl-Delta1-androsten-3-one (3) under the similar reaction conditions in good yield and single step reaction.     

Carbazole substituted N-acylated linear polyethylenimines (PEI). synthesis and characterization of poly[N-(9-carbazolyl)acetylethylenimine] and poly[N-(2-(9-carbazolyl))propanoylethylenimine]

The synthesis of carbazola substituted N-acylated polyethylenimines, namely, poly[N-(9-carbazolyl)acetylethylenimine] 20 and poly[N-(2-(9-carbazolyl))propanoylethylenimine] 21 by a grafting reaction onto PEI and isomerization polymerization of the carbazole substituted 2-oxazolines is reported. A complete acylation of amino groups in PEI by the 9-carbazolylacetyl groups was achieved by the p-nitrophenyl active ester method but PEI was only partially N-acylated by the 2-(9-carbazolyl)propanoyl groups under similar reaction conditions. The carbazole substituted 2-oxazolines, namely, 2-(9-carbazolyl)methyl-2-oxazoline 18 and (R,S)-2-[1-(9-carbazolyl)]ethyl-2-oxazoline 19 , were prepared by a base induced cyclization of ß-chloroamides. The ring-opening isomerization polymerization of 18 and 19 in the molten state with a cationic initiator (dimethyl sulfate, methyl triflate, or ethylene glycol ditosylate) gave 20 and 21. Gel permeation chromatography of 20 and 21 obtained with different monomerto-initiator ratios gave evidence of a chain transfer reaction with the monomer. The polymers were characterized by elemental analyses, IR, and ¹H-NMR spectroscopy.     

Indentation deformation/fracture of normal and anomalous glasses

Vickers deformation/fracture indentations have been investigated in six silicate glasses. The characteristic damage patterns fall into two distinct groups, according to whether the glass shows “normal” or “anomalous” mechanical behaviour. Observations of the damage morphology during and after contact, of the scales of the deformation and fracture zones, and of the residual stress intensity about the impressions, all point to a basic difference in the local stress/strain micromechanics. This difference is discussed in relation to the factors which control the brittleness of glass.     

Polyphenolic Profiling,Antioxidant, and Antimicrobial Activities Revealed the Quality and Adaptive Behavior of Viola Species,a Dietary Spice in the Himalayas

Background: Himalayan Viola species (Banksha) are traditionally important herbs with versatile therapeutic benefits such as antitussive, analgesic, antipyretic, antimalarial, anti-inflammatory, and anticancerous ones. The current investigation was focused on exploring polyphenolic profiles, antioxidant, and antimicrobial potentials of wild viola species at 15 gradient locations (375–1829 m). Methods: Morphological, physiochemical, and proximate analyses were carried out as per WHO guidelines for plant drug standardization. Total polyphenolic and flavonoid content were carried out using gallic acid and rutin equivalent. UPLC-DAD was used to profile the targeted polyphenols (gallic acid, vanillic acid, syringic acid, p-coumaric acid, ferulic acid, rutin, quercetin, luteolin, caffeic acid, and epicatechin). Similarly, all samples were screened for antioxidant and antimicrobial activity. Statistical analysis was used to correlate polyphenolic and targeted activities to assess Viola species adaptation behavior patterns. Results: Viola canescens (V. canescens) and Viola pilosa (V. pilosa) were found abundantly at their respective sites. Among flowers and leaves, flowers of V. canescens and V. pilosa showed higher total polyphenolic and flavonoid content (51.4 ± 1.13 mg GAE/g and 65.05 ± 0.85 mg RE/g, and 33.26 ± 0.62 mg GAE/g and 36.10 ± 1.41 mg RE/g, respectively). Furthermore, UPLC-DAD showed the uppermost content of p-coumaric acid in flowers and ferulic acid in leaves, while rutin was significant in both the tissues. Conclusions: The adaptive behavior of Viola species showed variability in morphological characters with the altitudes, while targeted polyphenols and activities were significant at mid-altitudes. This research helps in the selection of right chemotype for agrotechnological interventions and the development of nutraceutical products.     

Thermal and biological studies of Schiff bases of chitosan derived from heteroaryl aldehydes

Journal of Thermal Analysis and Calorimetry - The synthesis of Schiff bases of chitosan is performed by the reaction of chitosan with different heteroaryl aldehydes, i.e., furfuraldehyde,...