Simultaneous determination of nifuroxazide and drotaverine hydrochloride in pharmaceutical preparations by bivariate and multivariate spectral analysis.

The quantitative predictive abilities of the new and simple bivariate spectrophotometric method are compared with the results obtained by the use of multivariate calibration methods [the classical least squares (CLS), principle component regression (PCR) and partial least squares (PLS)], using the information contained in the absorption spectra of the appropriate solutions. Mixtures of the two drugs Nifuroxazide (NIF) and Drotaverine hydrochloride (DRO) were resolved by application of the bivariate method. The different chemometric approaches were applied also with previous optimization of the calibration matrix, as they are useful in simultaneous inclusion of many spectral wavelengths. The results found by application of the bivariate, CLS, PCR and PLS methods for the simultaneous determinations of mixtures of both components containing 2-12microgml(-1) of NIF and 2-8microgml(-1) of DRO are reported. Both approaches were satisfactorily applied to the simultaneous determination of NIF and DRO in pure form and in pharmaceutical formulation. The results were in accordance with those given by the EVA Pharma reference spectrophotometric method.

Application of derivative, derivative ratio, and multivariate spectral analysis and thin-layer chomatography-densitometry for determination of a ternary mixture containing drotaverine hydrochloride, caffeine, and paracetamol.

New selective, precise, and accurate methods are described for the determination of a ternary mixture containing drotaverine hydrochloride (I), caffeine (II), and paracetamol (III). The first method uses the first (D1) and third (D3) derivative spectrophotometry at 331 and 315 nm for the determination of (I) and (III), respectively, without interference from (II). The second method depends on the simultaneous use of the first derivative of the ratio spectra (DD1) with measurement at 312.4 nm for determination of (I) using the spectrum of 40 microg/mL (III) as a divisor or measurement at 286.4 and 304 nm after using the spectrum of 4 microg/mL (I) as a divisor for the determination of (II) and (III), respectively. In the third method, the predictive abilities of the classical least-squares, principal component regression, and partial least-squares were examined for the simultaneous determination of the ternary mixture. The last method depends on thin-layer chromatography-densitometry after separation of the mixture on silica gel plates using ethyl acetate-chloroform-methanol (16 + 3 + 1, v/v/v) as the mobile phase. The spots were scanned at 281, 272, and 248 nm for the determination of (I), (II), and (III), respectively. Regression analysis showed good correlation in the selected ranges with excellent percentage recoveries. The chemical variables affecting the analytical performance of the methodology were studied and optimized. The methods showed no significant interferences from excipients. Intraday and interday assay precision and accuracy values were within regulatory limits. The suggested procedures were checked using laboratory-prepared mixtures and were successfully applied for the analysis of their pharmaceutical preparations. The validity of the proposed methods was further assessed by applying a standard addition technique. The results obtained by applying the proposed methods were statistically analyzed and compared with those obtained by the manufacturer's method.

Application of spectrophotometric, densitometric, and HPLC techniques as stability indicating methods for determination of Zaleplon in pharmaceutical preparations.

Spectrophotometric, spectrodensitometric and HPLC are stability indicating methods described for determination of Zaleplon in pure and dosage forms. As Zaleplon is easily degradable, the proposed techniques in this manuscript are adopted for its determination in presence of its alkaline degradation product, namely N-[4-(3-cyano-pyrazolo[1,5a]pyridin-7-yl)-phenyl]-N-ethyl-acetamide. These approaches are successfully applied to quantify Zaleplon using the information included in the absorption spectra of appropriate solutions. The second derivative (D(2)) spectrophotometric method, allows determination of Zaleplon without interference of its degradate at 235.2 nm using 0.01N HCl as a solvent with obedience to Beer's law over a concentration range of 1-10 microg ml(-1) with mean percentage recovery 100.24+/-0.86%. The first derivative of the ratio spectra ((1)DD) based on the simultaneous use of ((1)DD) and measurement at 241.8 nm using the same solvent and over the same concentration range as (D(2)) spectrophotometric method, with mean percentage recovery 99.9+/-1.07%. The spectrodensitometric analysis allows the separation and quantitation of Zaleplon from its degradate on silica gel plates using chloroform:acetone:ammonia solution (9:1:0.2 by volume) as a mobile phase. This method depends on quantitave densitometric evaluation of thin layer chromatogram of Zaleplon at 338 nm over a concentration range of 0.2-1 microg band(-1), with mean percentage recovery 99.73+/-1.35. Also a reversed-phase liquid chromatographic method using 5-C8 (22 cm x 4.6 mm i.d. 5 microm particle size) column was described and validated for quantitation of Zaleplon using acetonitrile:deionised water (35:65, v/v) as a mobile phase using Paracetamol as internal standard and a flow rate of 1.5 ml min(-1) with UV detection of the effluent at 232 nm at ambient temperature over a concentration range of 2-20 microg ml(-1) with mean percentage recovery 100.19+/-1.15%. The insignificance difference of the proposed methods results with those of the reference one proved their accuracy and precision.

Simultaneous determination of hyoscine butylbromide and ketoprofen in pharmaceutical preparations by spectrophotometric and liquid chromatographic methods.

A binary mixture of hyoscine butylbromide and ketoprofen was determined by 4 different methods. The first involved determination of hyoscine butylbromide and ketoprofen using the ratio-spectra first-derivative spectrophotometric technique at 211 and 234 nm over the concentration ranges of 2-14 and 5-45 microg/mL with mean accuracies 99.84 +/-0.92 and 99.98+/- 0.64%, respectively. The second method utilized second-derivative spectrophotometry over the concentration ranges of 2-14 and 5-35 microg/mL with mean accuracies 99.32+/- 1.06 and 99.55+/-1.15%, respectively. The third method was based on the resolution of the 2 components by bivariate calibration depending on a simple and rapid mathematical algorithm and quantitative evaluation of the absorbances at 206 and 254 nm over concentration ranges of 2-16 and 5-35 microg/mL; mean accuracies of 100.21+/-1.30 and 100.19 +/-1.07% were obtained for hyoscine butylbromide and ketoprofen, respectively. The fourth method was reversed-phase liquid chromatography using 0.05 M ammonium dihydrogen phosphate-acetonitrile-methanol (20 + 30 + 6, v/v) as the mobile phase with ultraviolet detection at 220 nm over concentration ranges of 1-90 and 5-70 microg/mL; mean accuracies were 99.92+/-1.02 and 99.61+/- 0.98%, respectively. The suggested procedures were checked using laboratory-prepared mixtures and were successfully applied for the analysis of pharmaceutical preparations. The methods retained their accuracy and precision when the standard addition technique was applied. The results obtained by applying the proposed methods were statistically analyzed and compared with those obtained by the manufacturer's method.

Development and validation of three stability-indicating methods for determination of bisacodyl in pure form and pharmaceutical preparations.

Three new, simple, sensitive, and accurate stability-indicating methods were developed for quantitative determination of bisacodyl in the presence of its degradation products, monoacetyl bisacodyl (I) and desacetyl bisacodyl (II), in enteric coated tablets, suppositories, and raw material. The first is a spectrodensitometric method in which the drug is separated from I and II on silica gel plates using chloroform-acetone (9 + 1, v/v) as the mobile phase with ultraviolet detection of the separated bands at 223 nm over a concentration range of 0.2-1.4 microg/band for bisacodyl with mean recovery 100.35 +/- 1.923%. The second method is fourth derivative D4 spectrophotometry, which allows determination of bisacodyl in the presence of its degradation products in raw material at 223 nm using acetonitrile as the solvent with adherence to Beer's law over the concentration range 2-18 microg/mL with mean recovery 99.77+/-1.056%. In the third method, the spectrophotometric data of bisacodyl, I, and II using absolute ethanol as solvent were processed by 3 chemometric techniques: classical least-squares, principal component regression, and partial least-squares. A training set consisting of 15 mixtures containing different ratios of bisacodyl, I, and II was used for construction of the 3 models. A validation set consisting of 6 mixtures was used to validate the prediction ability of the suggested models. The 3 chemometric methods were applicable over a concentration range between 2-14microg/mL for bisacodyl with mean recovery of 99.97+/-0.865, 100.01 +/- 0.749, and 99.97 +/- 0.616% for the 3 models, respectively. The proposed methods were checked using laboratory-prepared mixtures and were successfully applied to the analysis of raw material and pharmaceutical formulations containing bisacodyl, except for the second method that applies only for raw material. The validity of the suggested procedures was further assessed by applying the standard addition technique; the recoveries obtained were in accordance with those given by the reference method.

Stability-indicating methods for determination of tiapride in pure form, pharmaceutical preparation, and human plasma.

Four different stability-indicating procedures are described for determination of tiapride in pure form, dosage form, and human plasma. Second derivative (D2), first derivative of ratio spectra (1DD), spectrofluorimetric, and high-performance column liquid chromatographic (LC) methods are proposed for determination of tiapride in presence of its acid-induced degradation products, namely 2-methoxy-5-(methylsulfonyl) benzoic acid and 2-diethylaminoethylamine. These approaches were successfully applied to quantify tiapride using the information included in the absorption, excitation, and emission spectra of the appropriate solutions. In the D2 method, Beer's law was obeyed in the concentration range of 1.5-9 microg/mL with a mean recovery of 99.94 +/- 1.38% at 253.4 nm using absolute ethanol as a solvent. In 1DD, which is based on the simultaneous use of the first derivative of ratio spectra and measurement at 245 nm in absolute ethanolic solution, Beer's law was obeyed over a concentration range of 1.5-9 microg/mL with mean recovery 99.64 +/- 1.08%. The spectrofluorimetric method is based on the determination of tiapride native fluorescence at 339 nm emission wavelength and 230 nm excitation wavelength using water-methanol (8 + 2, v/v). The calibration curve was linear over the range of 0.2-3 microg/mL with mean recovery of 99.66 +/- 1.46%. This method was also applied for determination of tiapride in human plasma. A reversed-phase LC method performed at ambient temperature was validated for determination of tiapride using methanol-deionized water-triethylamine (107 + 93 + 0.16, v/v/v) as the mobile phase. Sulpiride was used as an internal standard at a flow rate of 1 mL/min with ultraviolet detection at 214 nm. A linear relation was obtained over a concentration range of 2-30 microg/mL with mean recovery of 99.66 +/- 0.9%. Results were statistically analyzed and compared with those obtained by applying the reference method. They proved both accuracy and precision.

Determination of nifuroxazide and drotaverine hydrochloride in pharmaceutical preparations by three independent analytical methods.

Three new, different, simple, sensitive, and accurate methods were developed for quantitative determination of nifuroxazide (I) and drotaverine hydrochloride (II) in a binary mixture. The first method was spectrophotometry, which allowed determination of I in the presence of II using a zero-order spectrum with an analytically useful maximum at 364.5 nm that obeyed Beer's law over a concentration range of 2-10 microg/mL with mean percentage recovery of 100.08 +/- 0.61. Determination of II in presence of I was obtained by second derivative spectrophotometry at 243.6 nm, which obeyed Beer's law over a concentration range of 2-10 microg/mL with mean recovery of 99.82 +/- 1.46%. The second method was spectrodensitometry, with which both drugs were separated on a silica gel plate using chloroform-acetone-methanol-glacial acetic acid (6 + 3 + 0.9 + 0.1) as the mobile phase and ultraviolet (UV) detection at 365 nm over a concentration range of 0.2-1 microg/band for both drugs, with mean recoveries of 99.99 +/- 0.15 and 100.00 +/- 0.34% for I and II, respectively. The third method was reversed-phase liquid chromatography using acetonitrile-water (40 + 60, v/v; adjusted to pH 2.55 with orthophosphoric acid) as the mobile phase and pentoxifylline as the internal standard at a flow rate of 1 mU/min with UV detection at 285 nm at ambient temperature over a concentration range of 2-10 microg/mL for both drugs, with mean recoveries of 100.24 +/- 1.51 and 100.08 +/- 0.78% for I and II, respectively. The proposed methods were checked using laboratory-prepared mixtures and were successfully applied for the analysis of pharmaceutical formulations containing the above drugs with no interference from other dosage form additives. The validity of the suggested procedures was further assessed by applying the standard addition technique which was found to be satisfactory, and the percentage recoveries obtained were in accordance with those given by the EVA Pharma reference spectrophotometric method.

Spectrophotometric study of etodolac complexes with copper (II) and iron (III).

A rapid, simple, and selective method was developed for the determination of etodolac. The method depends on complexation of etodolac with copper (II) acetate and iron (III) chloride followed by extraction of complexes with dichloromethane and then measuring the extracted complexes spectrophotometrically at 684 and 385 nm in case of Cu (II) or Fe (III), respectively. Different factors affecting the reaction, such as pH, reagent concentration, and time, were studied. By use of Job's method of continuous variation, the molar ratio method, and elemental analysis, the stoichiometry of the reaction was found to be in the ratio of 1:2 and 1:3, metal:drug in the case of Cu (II) and Fe (III), respectively. The method obeys Beer's law in a concentration range of 2.00-9.00 and 0.50-2.00 mg/mL in case of Cu (II) and Fe (III), respectively. The stability of the complexes formed was also studied, and the reaction products were isolated for further investigation. The complexes have apparent molar absorptivities of about 32.14 +/- 0.97 and 168.32 +/- 1.12 for Cu (II) and Fe (III), respectively. The suggested procedures were successfully applied to the analysis of pure etodolac and its pharmaceutical formulations. The validity of the procedures was further ascertained by the method of standard additions, and the results were compared with other reported spectrophotometric methods and showed no significant difference in accuracy and precision.

New methods for determination of cinnarizine in mixture with piracetam by spectrodensitometry, spectrophotometry, and liquid chromatography.

Four new methods were developed and validated for the determination of cinnarizine HCl in its binary mixture with piracetam in pure and pharmaceutical preparations. The first one was a densitometric analysis that provides a simple and rapid method for the separation and quantification of cinnarizine HCI. The method depends on the quantitative densitometric evaluation of thin-layer chromatograms of cinnarizine HCI at 252 nm over concentration range of 1-6 microg/spot, with a mean accuracy of 100.05 +/- 0.91%. The second method was determination of the drug using a colorimetric method that utilizes the reaction of 3-methyl-benzothiazolin-2-one in the presence of FeCl3 as an oxidant. The green color of the resulting product was measured at 630 nm over concentration range 10-40 microg/mL, with a mean accuracy of 100.10 +/- 1.13%. The third method was a direct spectrophotometric determination of cinnarizine HCI at 252 nm over the concentration range 7-20 microg/mL, while piracetam was determined by derivative ratio spectrophotometry at 221.6 nm over concentration range 5-30 microg/mL, with a mean accuracy of 100.14 +/- 0.79 and 100.26 +/- 1.24% for cinnarizine HCI and piracetam, respectively. The last method was a liquid chromatography analysis of both cinnarizine HCI and piracetam, depending on quantitative evaluation of chromatograms of cinnarizine HCI and piracetam at 252 and 212 nm, respectively, over the concentration range 10-200 microg/mL for cinnarizine HCI and 20-500 microg/mL for piracetam, with a mean accuracy of 100.03 +/- 0.89 and 100.40 +/- 0.94% for cinnarizine HCI and piracetam, respectively. The proposed procedures were checked using laboratory-prepared mixtures and successfully applied for the analysis of their pharmaceutical preparations. The validity of the proposed procedures was further assessed by applying the standard addition technique. Recoveries were quantitative, and the results obtained agreed with those obtained by other reported methods.

Simultaneous determination of terbinafine HCL and triamcinolone acetonide by UV derivative spectrophotometry and spectrodensitometry.

A binary mixture of terbinafine hydrochloride and triamcinolone acetonide was determined by three different methods. The first one concerned with determination of both drugs using first derivative (D(1)) spectrophotometric technique at 297 and 274 nm over concentration ranges of 5-30 and 4-24 microg ml(-1), with mean percentage accuracies 99.90+/-0.67 and 100.25+/-0.49, respectively. The second method depends on ratio-spectra 1st derivative (RSD(1)) spectrophotometry at 298 and 248 nm over the same concentration ranges with mean percentage accuracies 100.22+/-0.51 and 99.93+/-0.56, respectively. The spectrodensitometric analysis provides a rapid and precise method for the separation and quantitation of both terbinafine hydrochloride and triamcinolone acetonide. The method depends on the quantitative densitometric evaluation of thin layer chromatogram of terbinafine hydrochloride and triamcinolone acetonide at 283 and 238 nm over concentration ranges of 5-25 and 2.5-22.5 microg spot(-1), with mean percentage accuracies 100.66+/-0.51 and 100.27+/-0.73, respectively. The suggested procedures were checked using laboratory prepared mixtures and were successfully applied for the analysis of their pharmaceutical preparations. The three methods retained their accuracy and precision when applying the standard addition technique. The results obtained by applying the proposed methods were statistically analysed and compared with those obtained by a reported method.