Shereen M. Galal

Use of Second Derivative Spectrophotometry For the Determination of Certain Cephalosporins and Their Acid-Induced Degradation Products In Combination

Abstract Methods for determination of individual cephalosporins and their corresponding acid-induced degradation products are described, based upon second derivative spectrophotometry. Linear plots of D2[dbnd](d2A/dλ2) values with negligible intercept were obtained versus concentration in the range of 0.4–2.4 mg% for both intact and degraded cephalosporins. Kinetic investigation of the cephalosporins degradation proved that the proposed method is applicable to stability determinations Compared with the official method the assay results of the different cephaiosporins pharmaceutical preparations were of equal accuracy (t-test) and reproducibility (F-test).

Non-parametric linear regression of discrete Fourier transform convoluted chromatographic peak responses under non-ideal conditions of internal standard method.

This manuscript discusses the application of chemometrics to the handling of HPLC response data using the internal standard method (ISM). This was performed on a model mixture containing terbutaline sulphate, guaiphenesin, bromhexine HCl, sodium benzoate and propylparaben as an internal standard. Derivative treatment of chromatographic response data of analyte and internal standard was followed by convolution of the resulting derivative curves using 8-points sin x(i) polynomials (discrete Fourier functions). The response of each analyte signal, its corresponding derivative and convoluted derivative data were divided by that of the internal standard to obtain the corresponding ratio data. This was found beneficial in eliminating different types of interferences. It was successfully applied to handle some of the most common chromatographic problems and non-ideal conditions, namely: overlapping chromatographic peaks and very low analyte concentrations. For example, a significant change in the correlation coefficient of sodium benzoate, in case of overlapping peaks, went from 0.9975 to 0.9998 on applying normal conventional peak area and first derivative under Fourier functions methods, respectively. Also a significant improvement in the precision and accuracy for the determination of synthetic mixtures and dosage forms in non-ideal cases was achieved. For example, in the case of overlapping peaks guaiphenesin mean recovery% and RSD% went from 91.57, 9.83 to 100.04, 0.78 on applying normal conventional peak area and first derivative under Fourier functions methods, respectively. This work also compares the application of Theils method, a non-parametric regression method, in handling the response ratio data, with the least squares parametric regression method, which is considered the de facto standard method used for regression. Theils method was found to be superior to the method of least squares as it assumes that errors could occur in both x- and y-directions and they might not be normally distributed. In addition, it could effectively circumvent any outlier data points. For the purpose of comparison, the results obtained using the above described internal standard method were compared with the external standard method for all types of linearity.

Spectrofluorimetric determination of guanethidine sulphate, guanoxan sulphate and amiloride hydrochloride in tablets and in biological fluids using 9,10-phenanthraquinone.

A highly sensitive spectrofluorimetric method for the determination of some drugs of the monosubstituted guanidine derivatives in laboratory made tablets, in spiked human serum and in urine samples is presented. The method is based on the reaction of guanethidine sulphate (I), guanoxan sulphate (II) and amiloride hydrochloride (III) with 9,10-phenanthraquinone (IV) to give highly fluorescent derivatives. The linearity ranges were found to be 0.06-0.96 mug/ml for (I) and (II) and 0.04-0.28 mug/ml for (III), with relative standard deviation less than 2%. Mean percentage recoveries for tablets were found to be 99.9 +/- 1.3, 100.5 +/- 1.1 and 100.0 +/- 1.6 for I, II and III, respectively. For I and III the results are highly correlated with the B.P. methods. Using the synchronous fluorimetry, differentiation between I and II was possible. Chloroform, dichloromethane and ethyl acetate have been used to extract I, II and III, respectively from serum and urine at basic pH, followed by applying the proposed fluorimetric method. Percentage recoveries were found to be 95.7-102.2%. The limit of detection is 0.04 mug/ml for I and II and 0.02 mug/ml for III.

Utility of Derivative Spectrophotometry For the Determination of Certain Cephalosporins and Their Alkali-Induced Degradation Products In Combination

Abstract First (D1-) and second (D2-) derivative spectrophotometric methods have been proposed for the assay of 7 cephalosporins, each with its alkali-induced degradation product in combination. Solutions of these cephalosporins in McIlvaines citric acid-phosphate buffer pH 7.0 were analyzed by measuring the 1st and 2nd derivative spectral response at certain wavelengths where the respective degradation products exhibit no contribution. the latter could be determined at the selected λ in the vicinity of negligible absorbance of the corresponding intact drug. Kinetic investigation of the alkaline degradation rate of cephalosporins revealed that the proposed methods were stability indicating. the different cephalosporin pharmaceutical preparations were assayed and gave results of equal accuracy (t-test)& reproducibility (F-test) with the corresponding official method of assay.

Comparative Spectrophotometrc Analysis of Rifampicin by Chelate Formation and Charge-Transfer Complexation

Abstract Simple, rapid, and accurate spectrophotometrc procedures for the determination of the antibiotic rifampicin, in capsules, are presented. A chelate formation of the antibiotic with cupric ion and charge-transfer complexation with halogenated quinones are carried out. Linear correlations between absorbance and concentration over the range of 40-100 μg ml−1 were computed. The reaction pathways were proposed. The utility of copper chelate as a stability indicating procedure as well as a method to determine rifampicin In spiked urine samples is demonstrated.

Fluorescence quenching method for the assay of three cephalosporins using the combined trigonometric function of Fourier series

The caphalosprirs: cefadroxil, cephaloxir, cephradine were assayed in their pharmaceutical preparations through the utility of mercurochrome fluorescence quesching phenomenon proceeding the alkaline degradation of cephalosporins

Spectroscopic Investigation of the Antazoune-p-chloranilic Acid Reaction Product

Abstract Spectroscopic studies on the reaction of p-chloranilic acid with antazoline base are reported. These include UV/VIS and IR spectrophotoraetry, electron spin resonance (ESR) and nuclear magnetic resonances (1H-NMR & 13C-NMR). The results reveal that the antazoline-p-chloranilic acid product is an ion pair salt rather than a charge-transfer complex.

Comparative study of some robust statistical methods: weighted, parametric, and nonparametric linear regression of HPLC convoluted peak responses using internal standard method in drug bioavailability studies

AbstractThis manuscript discusses the application and the comparison between three statistical regression methods for handling data: parametric, nonparametric, and weighted regression (WR). These data were obtained from different chemometric methods applied to the high-performance liquid chromatography response data using the internal standard method. This was performed on a model drug Acyclovir which was analyzed in human plasma with the use of ganciclovir as internal standard. In vivo study was also performed. Derivative treatment of chromatographic response ratio data was followed by convolution of the resulting derivative curves using 8-points sin xi polynomials (discrete Fourier functions). This work studies and also compares the application of WR method and Theils method, a nonparametric regression (NPR) method with the least squares parametric regression (LSPR) method, which is considered the de facto standard method used for regression. When the assumption of homoscedasticity is not met for analytical data, a simple and effective way to counteract the great influence of the high concentrations on the fitted regression line is to use WR method. WR was found to be superior to the method of LSPR as the former assumes that the y-direction error in the calibration curve will increase as x increases. Theils NPR method was also found to be superior to the method of LSPR as the former assumes that errors could occur in both x- and y-directions and that might not be normally distributed. Most of the results showed a significant improvement in the precision and accuracy on applying WR and NPR methods relative to LSPR. FigureComparison between RSD (percent) and Er (percent) calculated for Acyclovir, for area, D1, and D1/FF in the internal standard methods, using the three types of regression models: parametric, nonparametric, and weighted

Spectrofluorimetric determination of guanethidine sulphate, guanfacine hydrochloride, guanoclor sulphate and guanoxan sulphate in tablets and biological fluids, using benzoin

A sensitive and rapid Spectrofluorimetric method for the determination of guanethidine sulphate, guanfacine hydrochloride, guanoclor sulphate and guanoxan sulphate in tablets and spiked human serum and urine samples is described. The method is based on the reaction of monosubstituted guanidino compounds in an aqueous potassium hydroxide solution with benzoin, in the presence of β-mercaptoethanol and sodium sulphite. Highly fluorescent derivatives were obtained, with excitation and emission maximum wavelengths around 325 and 430 nm, respectively. In optimal reaction conditions, the linearity ranges were 0.04–0.28 μg/ml, with relative standard deviations less than 2%. The method has been successfully applied to the determination of these drugs in tablets. The results are highly correlated with the B.P. method. Chloroform (or for guanoxan dichloromethane) was used to extract the drugs from serum and urine at basic pH, followed by the proposed fluorimetric method. The limit of detection is 0.02 μg/ml for the selected drugs.

Spectrophotometric analysis of some guanidino drugs by acid-dye and charge-transfer complexation methods

Two spectrophotometric methods are described for the determination of guanethidine sulphate (I), guanfacine hydrochloride (II), guanoclor sulphate (III), guanoxan sulphate (IV) and debrisoquine sulphate (V). The first method involves ion-pair formation of the selected compounds (I-V) with bromocresol purple at pH 3.8. The yellow ion pair is extracted with chloroform and the absorbance is measured at about 415 nm. The second method is based on the reaction of the basic guanidino compounds (I, III-V) with iodine in chloroform to give molecular charge-transfer complexes with maximum absorbance at 292 and 345 nm. Beers law was obeyed for both methods and the relative standard deviations were found to be less than 2%. The apparent molar absorptivities were found to be 2.1 x 10(4) to 6.9 x 10(4) l mol-1 cm-1 using bromocresol purple and 0.7 x 10(4) to 2.4 x 10(4) l mol-1 cm-1 using iodine. The investigated drugs were assayed in tablets. The mean percentage recoveries were found to be 99.8-100.8% by the acid-dye method and around 100.4% by the charge-transfer complexation method.