Polarographic behaviour and determination of spironolactone

The polarographic behaviour of spironolactone in Britton-Robinson buffers containing 40% methanol as a solubilizer was studied. Over the pH range 3-12 a cathodic wave was produced. The wave was characterized as irreversible, diffusion-controlled and partially affected by adsorption phenomena. The number of electrons involved in the reduction was found by coulometric measurements at a controlled potential. A method was developed for the determination of spironolactone in tablets and the results obtained were in agreement with those obtained by the B.P. 1988 method. The mechanism of the electrode reaction is discussed.AvH scholar: 1989–1991     

Polarographic behaviour and determination of azintamide

Azintamide was found to be reduced at the dropping mercury electrode over the pH range 1.8–9.4 in Britton Robinson buffers containing 20% methanol. At pH 7.42 a well defined diffusion-controlled cathodic wave was produced. The limiting current versus concentration plot was linear over the range 0.025–1.0 mM and 0.005–1.0 mM in the DC_t and DPP modes, respectively, with a lower detection limit of 1 × 10^–7 M by the latter technique. A mechanism for the electrode reaction has been proposed. The method has been applied to the determination of azintamide in tablets, and the results obtained were in agreement with those obtained by a reference method.AvH Scholar 1989–1991.     

Experimental and theoretical approaches to the study of the reactivity and mechanism of the substitution of phenyl 1-(2,4-dinitronaphthyl) ether with anilines derivatives

Reactions of aniline derivatives in dimethyl sulfoxide with phenyl 1-(2,4-dinitronaphthyl) ether yield aryl 1-(2,4-dinitronaphthyl) amine, which results in substitution of the phenoxy groups at the naphthyl ipso carbon atom. Rate constants were measured spectrophotometrically, and reaction proton transfer was rate limiting. The values of the rate coefficients indicate a rate-limiting proton transfer mechanism with significant substituent effects. The calculated activation parameters were of regular variation with substituents in 4- and 3-position in the aniline nucleophile, and the reaction proceeded through a common mechanism. Hammett's reaction constant showed that the reaction rate constants depend on the electron density of the nitrogen atom of aniline derivative, whereas the coefficient value obtained from the Brönsted relation indicated that the reaction was significantly associative and quite zwitterion like. Computational studies of the substitution were carried out based on density functional theory, and theoretical to the experimental agreement was achieved.     

Synthesis of some new pyrimidine derivatives and evaluation of their anticancer and antibacterial activities

Starting from the reaction of ethyl cyanoacetate with thiourea and the appropriate aldehydes, a series of new pyrimidine derivatives were prepared. Ten selected pyrimidine derivatives were subjected to a screening system for the investigation of their antitumor potency against liver (HEPG2) cell line. The antitumor activity results indicated that most of the selected pyrimidine derivatives showed moderate growth inhibition activity against the tested cell line, but with varying intensities in comparison to the known anticancer drugs: 5-fluorouracil and doxorubicin. Some of the synthesized compounds were also tested for their antimicrobial activity against bacteria as well as fungal isolates.     

Determination of the Monoclonal Antibody Tocilizumab by a Validated Micellar Electrokinetic Chromatography Method

Chromatographia - Tocilizumab is a monoclonal antibody used in the treatment of several inflammatory and autoimmune diseases as well as cancers. Tocilizumab improves clinical outcomes and reduce...     

Kinetics of the Reaction of 2-Chloro-quinoxaline with Hydroxide Ion in ACN–H2O and DMSO–H2O Binary Solvent Mixtures

The kinetics of alkaline hydrolysis of 2-chloroquinoxaline (QCl) with hydroxide ion was investigated spectrophotometrically at different percentages of aqueous–organic solvent mixtures with acetonitrile (10–60% v/v) and with dimethylesulphoxide (10–80%) over the temperature range from 25 to 45 °C. The reaction was performed under pseudo first order conditions with respect to 2-chloroquinoxaline (QCl). An increase in the percentage of organic solvent (v/v) has different effects on the reaction rate constants, presumably due to hydrogen bond donor and acceptor differences of the media and other solvatochromic parameters. The data were discussed in terms of the Kamelt-Taft parameter and E _T(30). A nonlinear relation between the logarithm of the rate constant and reciprocal of the dielectric constant suggests the presence of selective solvation by the polar water molecules. Activation parameters ΔH ^#, ΔS ^# and ΔG ^# were determined and discussed.     

Simultaneous HPLC determination of thiocolchicoside and glafenine as well as thiocolchicoside and floctafenine in their combined dosage forms

Sensitive and accurate high-performance liquid chromatographic methods have been developed for the simultaneous determination of thiocolchicoside (TC)-glafenine (GF) (Mix I) and thiocolchicoside-floctafenine (FN) (Mix II) in their pharmaceutical formulations. The analysis for both mixtures was performed using 250 mm × 4.6 mm i.d., 5 μm particle size C18 Waters Symmetry column. The mobile phase consisted of methanol-0.035 M phosphate buffer (50:50, v/v) of pH 4.5 for Mix I and methanol-0.03 M phosphate buffer (70:30, v/v) of pH 4 for Mix II with flow rate of 1 mL/min and UV detection at 400 nm in both cases. The calibration plots were rectilinear over the concentration range of 0.2-2 μg/mL for TC in both mixtures and 20-200 μg/mL for each of GF and FN . The limits of detection for TC and GF were 0.05 μg/mL and 0.62 μg/mL, respectively, and for TC and FN were 0.02 μg/mL and 0.70 μg/mL, respectively. Additionally, the proposed methods were successfully applied to their combined tablets with average percentage recoveries of 100.35 ± 0.61 and 100.57 ± 0.72% for TC and GF respectively and for TC and FN the percentage recoveries were 101.2 ± 0.72 and 100.36 ± 0.67%, respectively. The results obtained were favorably compared with those given using the comparison methods.     

Efficient synthesis of α-substituted-α-arylmethyl phosphonates using trichloroacetimidate CC coupling method

A simple convenient protocol for the synthesis of diethyl α,α-diaryl methylphosphonate derivatives 5a-f, 6b-f, 7a-f and 8a-f, diethyl α-alkenyl α-aryl methylphosphonates 9a-d and 10a-d and α-(oxoalkyl) α-aryl methylphosphonate 11a-d and 12a-d is described. Trichloroacetimidates 3a-d were treated with activated arenes, styrene, allyltrimethylsilane or silylenol ethers C-nucleophiles in the presence TMSOTf to afford the desired products in good yields and short reaction time.     

Rapid micellar HPLC analysis of loratadine and its major metabolite desloratadine in nano-concentration range using monolithic column and fluorometric detection: application to pharmaceuticals and biological fluids

Background

Loratadine is a commonly used selective non-sedating antihistaminic drug. Desloratadine is the active metabolite of loratadine and, in addition, a potential impurity in loratadine bulk powder stated by the United States Pharmacopeia as a related substance of loratadine. Published methods for the determination of both analytes suffer from limited throughput due to the time-consuming steps and tedious extraction procedures needed for the analysis of biological samples. Therefore, there is a strong demand to develop a simple rapid and sensitive analytical method that can detect and quantitate both analytes in pharmaceutical preparations and biological fluids without prior sample extraction steps.

Results

A highly-sensitive and time-saving micellar liquid chromatographic method is developed for the simultaneous determination of loratadine and desloratadine. The proposed method is the first analytical method for the determination of this mixture using a monolithic column with a mobile phase composed of 0.15 M sodium dodecyl sulfate, 10% n-Butanol and 0.3% triethylamine in 0.02 M phosphoric acid, adjusted to pH 3.5 and pumped at a flow rate of 1.2 mL/min. The eluted analytes are monitored with fluorescence detection at 440 nm after excitation at 280 nm. The developed method is linear over the concentration range of 20.0–200.0 ng/mL for both analytes. The method detection limits are 15.0 and 13.0 ng/mL and the limits of quantification are 20.0 and 18.0 ng/mL for loratadine and desloratadine, respectively. Validation of the developed method reveals an accuracy of higher than 97% and intra- and inter-day precisions with relative standard deviations not exceeding 2%.

Conclusions

The method can be successfully applied to the determination of both analytes in various matrices including pharmaceutical preparations, human urine, plasma and breast milk samples with a run-time of less than 5 min and without prior extraction procedures. The method is ideally suited for use in quality control laboratories. Moreover, it could be a simple time-saving alternative to the official pharmacopeial method for testing desloratadine as a potential impurity in loratadine bulk powder.

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Graphical abstract Typical chromatogram of loratadine and its major metabolite desloratadine using the proposed micellar HPLC method