Determination of thiocolchicoside in its binary mixtures (thiocolchicoside-glafenine and thiocolchicoside-floctafenine) by TLC-densitometry.

The proposed method is based on TLC separation of thiocolchicoside from its binary mixtures (thiocolchicoside-glafenine and thiocolchicoside-floctafenine) followed by densitometric measurement at 375 nm. Separation was carried out on silica gel plates GF(254) using ethyl acetate:methanol:acetic acid (84:13:3%, v/v/v). Various conditions affecting separation and measurement were studied and optimized. Calibration was performed using third-order polynomial equation. It was found superior to first-order with respect to quantification range (0.25-25 microg per spot), correlation coefficient and standard error of estimation. The proposed method was successfully applied for the determination of thiocolchicoside in its synthetic binary mixtures and commercial tablets. Results were compared with those obtained by reference methods and non-significant difference was obtained regarding accuracy and precision. Assay precision using two-way ANOVA was performed on results of inter- and intra-day applications of the method.

Kinetic study of alkaline induced hydrolysis of the skeletal muscle relaxant chlorzoxazone using ratio spectra first derivative spectrophotometry.

2-Amino-4-chlorophenol was found to be the alkaline induced degradation product and the synthetic precursor of chlorzoxazone. The aim of this work is to study different factors affecting the degradation process due to the high toxicity of 2-amino-4-chlorophenol. Chlorzoxazone was found to follow pseudofirst order kinetics. Ratio spectra first derivative spectrophotometry (DR(1)) was developed for monitoring the change in chlorzoxazone concentration during the degradation process. Kinetic parameters (rate constant (K) and half-life (t(0.5))) were calculated at different temperatures (40-120 degrees C) and different sodium hydroxide concentrations (3-10 M). Activation energy at 3 and 8 M sodium hydroxide concentration and alkaline induced catalysis constant at 60, 70 and 80 degrees C were also calculated.

Stability indicating methods for the determination of loratadine in the presence of its degradation product.

Four stability-indicating procedures have been suggested for determination of the non sedating antihistaminic agent loratadine. Loratadine being an ester undergoes alkaline hydrolysis and the corresponding acid derivative is produced as a degradation product. Its identity was confirmed using IR and MS. The first procedure is based on determination of loratadine by HPLC with detection at wavelength, 250 nm. Mobile phase is acetonitrile:orthophosphoric acid (35:65) using benzophenone as an internal standard. Sensitivity range is 5.00-50.00 microg/ml. Second determination is a densitometric procedure based on determination of loratadine in the presence of its degradate at lambda 246 nm using the mobile phase; methanol:ammonia (10:0.15). Sensitivity range is 1.25-7.50 microg per spot. The third procedure is a spectrophotometric one where a mixture of loratadine and its degradate are resolved by first derivative ratio spectra. Sensitivity range is found to be 3.00-22.00 microg/ml, upon carrying out the measurements at wavelengths 236, 262.4 and 293.2 nm. The fourth procedure is based on second derivative spectrophotometry, where D(2) measurements are carried out at lambda 266 nm. The sensitivity range is 3.00-22.00 microg/ml. The validity of the described procedures was assessed by applying the standard addition technique. Statistical analysis of the results have been carried out revealing high accuracy and good precision. The suggested procedures could be used for determination of loratadine both in pure and dosage forms, as well as in the presence of its degradate.

Stability indicating methods for assay of mequitazine in presence of its degradate.

Six procedures have been suggested for the determination of the antihistaminic agent, mequitazine, in the presence of its degradate. Mequitazine, having a phenothiazine group, undergoes peroxide oxidation and the corresponding sulphone is produced. Its identity was confirmed by IR and MS. The first procedure is based on determination of mequitazine by HPLC with UV detection at 256 nm. The mobile phase used is acetonitrile, ortho phosphoric acid (50:50) using caffeine as an internal standard. Linearity range is 1.00-9.00 microg/ml. The second determination is a densitometric procedure based on the determination of mequitazine in the presence of its degradate at 256 nm using the mobile phase, chloroform:methanol:ammonia (50:18:3). Linearity range is 1.25-7.50 microg per spot. The third procedure is spectrophotometric, where a mixture of mequitazine and its degradate are resolved by first derivative ratio spectra. Linear calibration graphs of first derivative values at wavelengths 210.2, 247 and 259.8 nm are obtained. On carrying out measurements at the three mentioned wavelengths, the linearity range is found to be 1.00-10.00 microg/ml. The fourth procedure is based on first derivative spectrophotometry, where D(1) measurements are carried out at 290 nm. Linearity range is 1.00-10.00 microg/ml. The fifth procedure is based on the reaction of mequitazine with 3-methyl-2-benzothiazolinone hydrazone (MBTH) in the presence of ferric chloride. A stable violet colored oxidative coupling product is formed, which is measured spectrophotometrically at 685 nm. The optimum experimental parameters for the reaction have been studied and assigned. Linearity range is 1.00-16.00 microg/ml. The sixth procedure is based on the reaction of mequitazine in the presence of its degradate with 2,6-dichloroquinone-4-chloroimide (Gibbs reagent) in aqueous methanolic medium. The reddish-brown colored condensation product is measured at 405 nm. The optimum experimental conditions for the reaction have been studied. Linearity range is 50.00-600.00 microg/ml. The validity of the described procedures was assessed by applying the standard addition technique. Statistical analysis of the results has been carried out revealing high accuracy and good precision. The suggested procedures could be used for the determination of mequitazine, both in pure and dosage forms, as well as in the presence of its degradate.

Investigation of ketoconazole copper(II) and cobalt(II) complexes and their spectrophotometric applications.

Ketoconazole, as a ligand, reacts quantitatively with copper(II) and cobalt(II) to form blue-colored, stable complexes in dichloromethane. These complexes can be spectrophotometrically measured at 720 and 612.5 nm in the case of Cu(II) or Co(II), respectively. Different factors affecting the reaction such as pH, reagent concentration, solvent effect, and time were studied. By using Job's method of continuous variation, the stoichiometry of the reaction was found to be in the ratio of 1:2, metal:drug, with Cu(II) and Co(II). The stability of the complexes formed was also studied. The reaction products were isolated for further investigation. The complexes have apparent molar absorptivities of 35.36 +/- 1.95 and 59.62 +/- 1.87 for Cu(II) and Co(II), respectively. Suggested procedures based on the stoichiometric reaction were successfully applied to the analysis of the pure drug and its pharmaceutical formulations. The validity of the procedures was further ascertained by the method of standard additions. The developed method was found to be simple, accurate, and precise when compared with the official method of the British Pharmacopoeia.

Stability indicating method for determination of nortriptyline hydrochloride using 3-methyl-2-benzothiazolinone hydrazone (MBTH).

A spectrophotometric procedure is described for determination of nortriptyline hydrochloride in pure and dosage form as well as in the presence of its degradate. 3-Methyl-2-benzothiazolinone hydrazone (MBTH) has been used as the chromogenic reagent, where aqueous solutions of the drug and reagent are treated with cerium(IV) ammonium sulphate in an acidic medium. Nortriptyline hydrochloride reacts to give a blue coloured product having two absorption maxima at 619 and 655 nm. Various parameters affecting the reaction have been studied. Beer's law is obeyed in the concentration range of 24-216 microg ml(-1) of nortriptyline hydrochloride, with mean percentage recoveries of 100.22+/-0.870 and 100.66+/-0.642% for both maxima, 619 and 655 nm, respectively. Results were statistically analyzed and compared with those obtained by applying the British Pharmacopoeia (1993) method.