Stability-indicating high performance liquid chromatographic determination of raubasine in its binary mixture with kinetic study of raubasine acid degradation.

Stability-indicative determination of raubasine (RAB) in the presence of its degradate and its binary mixture with almitrine dismesylate (ALM) was investigated. The degradation product had been isolated, via acid-degradation, characterized and confirmed. Selective quantification of RAB and ALM in bulk form, pharmaceutical formulations and/or in the presence of RAB degradate was demonstrated. The analytical technique adopted for quantification was high performance liquid chromatography (HPLC). Separation was performed using a ZORBAX ODS column with a mobile phase consisting of acetonitrile+phosphate buffer pH 3.4 80:20 (v/v) with UV detection at 254 nm. The method showed high sensitivity with good linearity over the concentration range of 5-120 and 5-60 µg mL(-1) for RAB and ALM respectively. The HPLC method was used to study the kinetics of RAB acid degradation that was found to follow a first-order reaction. The activation energy could be estimated from the Arrhenius plot and it was found to be 18.152 kcal mol(-1).

Stability-indicating chemometric methods for the determination of pyritinol dihydrochloride.

Three multivariate calibration methods, including classical least square with nonzero intercept (CLS), principal component regression (PCR) and partial least square (PLS), have been used for the determination of pyritinol dihydrochloride in the presence of its degradation product. The CLS, PCR and PLS techniques are useful in spectral analysis because the simultaneous inclusion of many spectral wavelengths instead of the single wavelength used in derivative spectrophotometry has greatly improved the precision and predictive abilities of these multivariate calibrations. A training set was constructed for the mixture and the best model was used for the prediction of the concentration of the selected drug. The proposed procedures were applied successfully in the determination of pyritinol dihydrochloride in laboratory-prepared mixtures and in commercial preparations. Pyritinol dihydrochloride was analysed with mean accuracies 99.99 +/- 0.905, 99.91 +/- 0.966 and 99.92 +/- 0.962 using the CLS, PCR and PLS methods respectively. The validity of the proposed methods was assessed using the standard addition technique. The proposed procedures were found to be rapid and simple and required no preliminary separation. They can therefore be used for the routine analysis of pyritinol dihydrochloride in quality-control laboratories.

Stability-indicating methods for the determination of a mixture of almitrine and raubasine by derivative spectrophotometry.

A second-derivative spectrophotometric method ((2)D) and a derivative ratio spectrum zero crossing ((1)DD) method were used to determine raubasine and almitrine dismesylate in the presence of raubasine degradation product, using methanol as a solvent. Linear relationships were obtained in the range from 6-20 microg ml(-1) raubasine for the ((2)D) method and 12-24 microg ml(-1) almitrine dismesylate for the ((1)DD) method. By applying these methods it was possible to determine raubasine in its pure powdered form with an accuracy of 99.93 +/- 1.116 (n = 8) for the ((2)D) method and almitrine dismesylate with an accuracy of 99.98 +/- 0.602 (n = 7) for the ((1)DD) method.Laboratory-prepared mixtures containing different ratios of raubasine, almitrine dismesylate and raubasine degradation product were analysed and the proposed methods were valid up to 50% of raubasine degradation product. They were found to be suitable stability-indicating assay methods for raubasine and almitrine dismesylate in pharmaceutical formulations.

Smart stability-indicating spectrophotometric methods for determination of binary mixtures without prior separation.

Ratio subtraction and isosbestic point methods are 2 innovating spectrophotometric methods used to determine vincamine in the presence of its acid degradation product and a mixture of cinnarizine (CN) and nicergoline (NIC). Linear correlations were obtained in the concentration range from 8-40 microg/mL for vincamine (I), 6-22 microg/mL for CN (II), and 6-36 microg/mL for NIC (III), with mean accuracies 99.72 +/- 0.917% for I, 99.91 +/- 0.703% for II, and 99.58 +/- 0.847 and 99.83 +/- 1.039% for III. The ratio subtraction method was utilized for the analysis of laboratory-prepared mixtures containing different ratios of vincamine and its degradation product, and it was valid in the presence of up to 80% degradation product. CN and NIC in synthetic mixtures were analyzed by the 2 proposed methods with the total content of the mixture determined at their respective isosbestic points of 270.2 and 235.8 nm, and the content of CN was determined by the ratio subtraction method. The proposed method was validated and found to be suitable as a stability-indicating assay method for vincamine in pharmaceutical formulations. The standard addition technique was applied to validate the results and to ensure the specificity of the proposed methods.

Stability-indicating methods for determination of vincamine in presence of its degradation product.

Three different stability indicating assay methods are developed and validated for determination of vincamine in the presence of its degradation product (vincaminic acid). The first method is based on the derivative ratio zero crossing spectrophotometric technique using 0.1 N hydrochloric acid as a solvent. In the second method, measurements are based on spectro-densitometric technique using high performance thin-layer chromatography (HPTLC) plates with a developing system consisting of methanol-chloroform-ethyl acetate (2:1:1, v/v/v). The third method depends on high-performance liquid chromatography (HPLC). Separation of vincamine from vincaminic acid using Lichrocart RP-18 column (250 mm x 4.6 mm i.d.) with a mobile phase consisting of acetonitrile-ammonium carbonate (0.01 M) (7:3, v/v) is achieved. The methods showed high sensitivity with good linearity over the concentration ranges of 12 to 48 microg ml-1, 3 to 17 microg/spot, and 2 to 20 microg ml-1 for derivative spectrophotometry, spectro-densitometry and HPLC methods, respectively. The developed methods were successfully applied to the analysis of pharmaceutical formulations containing vincamine with excellent recoveries.

Stability-indicating methods for determination of pyritinol dihydrochloride in the presence of its precursor and degradation product by derivative spectrophotometry.

A first-derivative spectrophotometric (1D) method and a derivative-ratio zero-crossing spectrophotometric (1DD) method were used to determine pyritinol dihydrochloride (I) in the presence of its precursor (II) and its degradation product (III) with 0.1N hydrochloric acid as a solvent. Linear relationships were obtained in the ranges of 6-22 microg/mL for the (1D) method and 6-20 microg/mL for the (1DD) method. By applying the proposed methods, it was possible to determine pyritinol dihydrochloride in its pure powdered form with an accuracy of 100.36 +/- 1.497% (n = 9) for the (1D) method and an accuracy of 99.92 +/- 1.172% (n = 8) for the (1DD) method. Laboratory-prepared mixtures containing different ratios of (I), (II), and (III) were analyzed, and the proposed methods were valid for concentrations of < or = 10% (II) and < or = 50% (III). The proposed methods were validated and found to be suitable as stability-indicating assay methods for pyritinol in pharmaceutical formulations.