Mohamed A. Korany

High performance liquid chromatographic determination of some co-administered anticancer drugs in pharmaceutical preparations and in spiked human plasma.

Two HPLC methods are introduced in this paper for the simultaneous determination of doxorubicin hydrochloride (DOX) and 5-fluorouracil (5-FU), combination I, and of cytarabine (CYT) and etoposide (ETO), combination II, as co-administered drugs. In both combinations, a [250 mm x 4.6 mm C-18 column is used. The mobile phase for combination I consists of a mixture of acetonitrile and 0.05 M disodium hydrogenphosphate (50:50, v/v) containing 0.1% sodium laurylsulfate (SLS) adjusted to pH 3.7 at a flow rate 1 ml/min, with UV detection at 260 nm and ambient temperature. For combination II, the mobile phase consists of a mixture of 0.02 M sodium dihydrogenphosphate aqueous solution adjusted to pH 6.0 (with 0.2 M orthophosphoric acid or sodium hydroxide) and acetonitrile in a ratio of (7:3) at a flow rate 1 ml/min, with UV detection at 254 nm and ambient temperature. The methods also permitted the determination of methyl hydroxybenzoate (MHB) which is used as a preservative in DOX vials, combination I, and of benzyl alcohol (BZA) preservative in ETO vials, combination II. The proposed HPLC methods were successfully applied to the determination of the investigated drugs, of the two combinations, both in injection solutions and spiked human plasma samples with high precision and accuracy. Linearity, validation, accuracy, precision, limits of detection, limits of quantitation, and other aspects of analytical validation are presented in the text.

Application of orthogonal functions to spectrophotometric analysis of weakly absorbing compounds in tablets.

Glenns method of orthogonal functions has been applied to correct for irrelevant absorption during the analysis of tablets of chlorpheniramine maleate, phenyltoloxamine dihydrogen citrate, diphenhydramine hydrochloride and ephedrine hydrochloride. The results suggest that the method can be used for routine analysis.

Colorimetric Determination of Seven Nonsteroidal Antiinflammatory Drugs Using 2-Nitrophenylhydrazine Hydrochloride

Abstract A simple, sensitive and convenient colorimetric method for the determination of seven nonsteroidal anti-inflammatory drugs, namely, flufenamic acid, mefenamic acid, niflumic acid, ketoprofen, ibuprofen, diclofenac sodium and indomethacin, was developed. The method is based on reaction of the abovementioned compounds - being carboxilic compounds, reacting with 2-nitrophenylhydrazine in presence of diclohexylcarbodiimide in ethanolic medium to give acid hydrazine, which showed intense violet colour with a maximum absorption at around 550 nm. The effect of reagent concentration (2-nitrophenylhydrazine hydrochloride, pyridine and dicyclohexylcarbodiimide), heating temperature and heating time were studied to optimize reaction conditions. The method was successfully applied to the determination of those drugs in pure and dosage forms, with a relative standard deviation less than 2%.

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).

Computer-assisted spectrophotometry: multicomponent analysis with a discrete fourier transform.

A computer-assisted method for analysis of multicomponent mixtures by use of conventional absorbance as well as discrete Fourier transforin coefficients (combined trigonometric functions) is presented. The program can store absorbance data (A vs. lambda), process data by convolution with combined trigonometric functions, apply least-squares analysis and solve the resultant simultaneous linear equations, and display data on screen, printer or plotter.

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.

Non-parametric linear regression of discrete fourier transform convoluted chromatographic peak responses in non-ideal conditions

This manuscript discusses the application of chemometrics to the handling of HPLC response data using a model mixture containing ascorbic acid, paracetamol and guaiphenesin. Derivative treatment of chromatographic response data followed by convolution of the resulting derivative curves using 8-points sinx(i) polynomials (discrete Fourier functions) was found beneficial in eliminating different types of interferences. This was successfully applied to handle some of the most common chromatographic problems and non-ideal conditions, namely: very low analyte concentrations, overlapping chromatographic peaks and baseline drift. For example, a significant change in the correlation coefficient of guaiphenesin, in case of baseline drift, went from 0.9978 to 0.9998 on applying normal conventional peak area and first derivative under Fourier functions methods, respectively. It also compares the application of Theils method, a non-parametric regression method, in handling the response 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.

Derivative spectrophotometric determination of glibenclamide, mebeverine hydrochloride and clopamide in the presence of their alkaline-induced degradation products

First- and second-derivative spectrophotometric methods have been proposed for the determination of glibenclamide, mebeverine hydrochloride and clopamide with their corresponding degradation products. Solutions of these drugs were analysed by measuring the first- and second-derivative spectral response at certain wavelengths where the respective degradation products exhibit no contribution. Also, clopamide can be determined in a mixture with reserpine and dihydroergocristine by utilising the second-derivative method. Kinetic investigation of the alkaline degradation rate of these drugs revealed that the proposed methods were stability indicating. The different pharmaceutical preparations were assayed and were found to give results of the same accuracy and reproducibility as the corresponding official method or “maximum absorbance” methods of assay.

First derivative spectrophotometric and high-performance liquid chromatographic determination of cinchocaine hydrochloride in presence of its acid degradation product

Two methods are presented for the determination of cinchocaine HCl in presence of its acid-induced degradation product using first (1D) derivative spectrophotometry and high-performance liquid chromatography. Cinchocaine HCl was determined by measurement of its first derivative amplitude at the zero crossing point of 2-hydroxyquinoline-4-carboxylic acid diethylaminoethylamide as its acid degradation product (at 333.5 nm). The HPLC method depends upon using a mu Bondapak C18 column at ambient temperature with a mobile phase consisting of acetonitrile--0.01 M sodium acetate trihydrate (45:55, v/v) containing 0.06% (w/v) heptane sulphonic acid sodium salt and adjusted to apparent pH 4.5 with acetic acid at a flow rate 2 ml min-1. Quantitation was achieved with UV detection at 254 nm based on peak area. The HPLC method was applied for simultaneous determination of cinchocaine HCl, methylparaben and propylparaben. The two proposed methods were successfully applied to the determination of the cinchocaine HCl in laboratory-prepared mixtures in the presence of its acid degradation product and in cream. Moreover, the proposed methods were utilized to investigate the kinetics of the acid degradation process at different temperatures and the apparent pseudo first-order rate constant, half-life and activation energy calculated.

Colorimetric determination of some penicillins and cephalosporins with 2-nitrophenylhydrazine hydrochloride.

A simple and sensitive calorimetric method for the determination of some penicillins and cephalosporins is presented. The method is based on reaction with 2-nitrophenylhydrazine hydrochloride in presence of dicyclohexylcarbodi-imide and pyridine. The violet colour of the resulting acid hydrazide is measured at the appropriate wavelength. The method has been applied to determination of these antibiotics in bulk and dosage forms, with a coefficient of variation less than 2%.