Non-aqueous electromigration analysis of some degradation products of carvedilol

A capillary electrophoresis method was used for assay of some degradation products of carvedilol. The optimized parameters were as; running buffer 80 mM acetate dissolved in methanol/ethanol mixture [65:35% v/v], applied voltage of 19 kV, temperature is 20 °C and the wavelength range of 200-350 nm. The results indicate that the proposed capillary electrophoresis method could effectively separate carvedilol from its degradation products and can be employed as a stability indicating assay method. In addition, the presence of a new unknown degradation product was discovered by this method. In addition, capillary electrophoresis behaviour of carvedilol in photo/force degradation conditions gave valuable information concerning the dissimilarities of their ionization. Results indicated that the proposed method can be used for the determination of carvedilol in human serum. Finally, accuracy of the proposed method was established by recovery experiments from spiked human serum samples

stability indicating capillary electrophoresis method for analysis of buserelin

A simple and rapid stability indicating method based on capillary zone electrophoresis has been developed and validated for the analysis of buserelin [BUS]. The best separations were achieved by using a bare fused silica capillary [75 microm i.d.; 65.5 cm total, 57.0 cm effective length], phosphate buffer [pH = 3.00; 26.4 mM], at 35°C. The sample was hydrodynamically injected at 50 mbar for 5 seconds; the applied voltage was 30 kV and detection was carried out by UV-absorbance at 200 nm. Method validation resulted in the following figures of merit: the method was linear in the concentration range between 0.781 and 500 microg/ml [linear regression coefficient 0.9996], accuracy was between 99.3% and 100.9%, intra assay precision was between 0.3% and 1.0% and intermediate precision was between 1.0% and 2.1%. Evaluation of the specificity of the method showed no interference between excipients or products of force degradation and BUS. Under the selected conditions, separation of BUS and its degradation products was completed in less than 10 min, and BUS could be quantified after different stress conditions without any interference. The results enabled the conclusion that under thermal stress upon exposure to 90°C BUS is degraded by first order kinetics. It was demonstrated that the method can be applied as a rapid and easy to use method for quantification and stability testing of BUS in biopharmaceutical formulations in quality control laboratories

Effect of pioglitazone on plasma levels of phenytoin in rats

Introduction: Interaction between drugs represents a major clinical concern for health care professionals and their patients. Patients affected by both type 2 diabetes and epilepsy may be prescribed pioglitazone and an anti-epileptic drug such as phenytoin concurrently. The aim of this study was to consider the interaction of pioglitazone with phenytoin in an experimental model. According to the result of this study concurrent use of phenytoin and pioglitazone in clinic may cause therapeutic failure of phenytoin which may cause seizures and during seizures the cardiac function may be affected

Materials and Methods: Two groups of rats were treated for 30 days. In group 1 [control group] saline [10 ml/kg] and phenytoin [30 mg/kg] were administered daily by intragastric gavage. In group 2 [test group], pioglitazone [10 mg/kg] was administered daily 60 minutes before phenytoin [30 mg/kg]. Two hours after the last intragastric gavage, animals were anesthetized with ether and 2 ml of blood was drawn from the heart into a syringe containing Ethylenediaminetetraacetic [EDTA], and phenytoin concentration in rat plasma was determined by High performance liquid chromatography [HPLC].The study consisted of 2 groups of 10 male adult Wistar rats

Results: Compared with control group, concurrent use of pioglitazone and phenytoin was associated with significantly lower mean plasma concentrations of phenytoin: 2.08 +/- 0.25 micro g/ml VS 1.2 +/- 0.02 micro g/ml [p< 0.05]

Conclusion: Concurrent use of pioglitazone and phenytoin was associated with a significant decrease in plasma concentration of phenytoin in this experimental model. In clinic, this interaction may cause seizures and it has been shown that both cardiac and respiratory functions may affected by seizures

Development and validation of a terbium-sensitized luminescence analytical method for deferiprone

A sensitive fluorometric method for the determination of deferiprone [DFP] based on the formation of a luminescent complex with Tb[3+] ions in aqueous solutions is reported. The maximum excitation and emission wavelengths were 295 and 545 nm, respectively. The effects of various factors on the luminescence intensity of the system were investigated and optimized, then under the optimum conditions, the method was validated. The method validation results indicated that the relative intensity at 545 nm has a linear relationship with the concentration of DFP in aqueous solutions at the range of 7.2 x 10[-9] to 1.4 x 10[-5] M, the detection and quantification limits were calculated respectively as 6.3 x 10[-9] and 2.1 x 10[-8] M, precision and accuracy of the method were lower than 5% and the recovery was between 100.1% and 102.3%. The results indicated that this method was simple, time saving, specific, accurate and precise for the determination of DFP in aqueous solutions. After optimization and validation, the method successfully applied for determination of DFP in tablet dosage forms. The stoichiometry of the Tb[3+]-DFP complex was found as 1:3 and the complex formation constant was 1.6 x 10[16]

Modeling the solvatochromic parameter [E[NT]] of mixed solvents with respect to solvent composition and temperature using the Jouyban-acree model

Applicability of the Jouyban-Acree model for calculation of solvatochromic parameter [E [N/T]] of binary solvents at various temperatures has been shown by employing 12 experimental data sets collected from the literature. The accuracy of the model was evaluated by calculating average percentage deviation [APD] between calculated and observed values. The obtained overall APD [ +/- S.D.] were 1.2 [ +/- 0.9] and 2.2 [ +/- 1.8]%, respectively for correlative and predictive analyses

Solubility prediction of sulfonamides at various temperatures using a single determination

Solubility of sulphamethoxazole, sulphisoxazole and sulphasalazine in six solvents namely water,methanol, ethanol, 1-propanol, acetone and chloroform were determined at 15, 25, 37 and 45 °C. Two models derived from the Hildebrand solubility approach are proposed for solubility prediction at different temperatures using a single determination. The experimental data of the present work as well as data gathered from the literature have been employed to investigate the accuracy and prediction capability of the proposed models. The overall percent deviations between the predicted and experimental values were 10.78 and 14.63% which were comparable to those of the classical two and three parameter models. The proposed models were much superior to the two pure predictive models i.e., the ones which do not require experimental solubility determination, as the overall percent deviations produced by the latter models were 150.09 and 161.00%

Application of the phenomenological model to electrophoretic mobility in mixed solvent electrolyte systems in capillary zone electrophoresis

The phenomenological model of Khossravi and Connors [1992] has been adopted to calculate the electrophoretic mobility of drugs at different concentrations of solvents in a binary mixture. The accuracy and predictability of the model have been evaluated employing 14 experimental data sets by using average percentage mean deviation [APMD]. The obtained APMD for correlative and predictive studies are within an acceptable error range and the results show that the model can be used in method development stage to speed up the optimisation process

Mathematical representation of electrophoretic mobility in ternary solvent electrolyite systems

Electrophoretic mobilities of salmeterol and phenylpropanolamine in capillary zone electrophoresis were determined using acetate buffer in mixed solvents containing different concentrations of water, methanol and acetonitrile. Maximum electrophoretic mobilities for salmeterol and phenylpropanolamine were observed with water-methanol-acetonitrile ratios of 5:50:45 v/v and 3:60:37 v/v, respectively, and minimum mobilities of both compounds occurred in methanol-acetonitrile ratio of 30:70 v/v. The generated experimental data have been used to evaluate a mathematical model to compute the electrophoretic mobility of the analytes in a ternary solvent electrolyte system. The proposed model is: ln micro m = Function1 ln micro 1+ Function2 ln micro 2+k Function3+M1 Function1 Function2+M2 Function1 Function3+M3 Function2 Function3+M4 Function1 Function°1+M5 Function°2 Function3+M6 Function°2 Function3+M7 Function1 Function2 Function3. Where micro is the electrophoretic mobility, subscripts m,1, 2 and 3 refer to mixed solvent and solvents 1-3, respectively, f is the volume fraction of the solvent in the mixed solvent system and M1-M7 and K are the model constants calculated by a least squares analysis. The generated experimental data fitted to the model and the back-calculated mobilities were employed to compute the average percentage deviation [APD] as an accuracy criterion. The obtained APD for salmeterol and phenylpropanolamine are 3.10 and 2.21%, respectively and the low APD values indicate that the model is able to calculate the mobilities within an acceptable error range

Modelling the electrophoretic mobility of basic drugs in aqueous-methanolic buffers in capillary electrophoresis

The electrophoretic mobility of three beta-blocker drugs, i.e. nadolol, oxprenolol and pindolol, in sodium acetate buffer containing different concentrations of methanol varying from 0 to 100% have been determined by a capillary electrophoresis instrument. The generated experimental data have been employed to evaluate the accuracy of a mathematical model to calculate the electrophoretic mobility at different concentrations of methanol. The proposed model is: In micro m=[function]c In micro c+[function]w In micro w+K1 [function]c [function]w+K2 [function]°C fw. Where micro is the electrophoretic mobility, ' is the volume fraction, subscripts m, c and w are the mixed water-methanol, pure methanol and pure water, respectively, K1 and K2 are the model constants. The proposed model produced accurate results and the average percentage deviation between experimental and calculated mobilities was 1.21% for the data sets studied. This percentage error could be considered as an acceptable error where the relative standard deviation for the repeated experiments is around 2%