Kamal E. E. Ibrahim

Sequential injection technique for automated titration: Spectrophotometric assay of vitamin C in pharmaceutical products using cerium(IV) in sulfuric acid

For the first time sequential injection analysis (SIA) technique has been employed for titrimetry. A new SI titrimetric spectrophotometric method for the assay of vitamin C in drug formulations was explored. The method is based on the oxidation reaction of vitamin C with cerium(IV) in sulfuric acid media using a spectrophotometer as a detector with the wavelength monitored at 410 nm. A 2(3) factorial design chemometric approach was employed to study the interaction effect of the chemical and system variables, mainly cerium(IV), sulfuric acid concentrations and the flow rate. The results of the chemometric optimization revealed that the optimum operating conditions for the SI titrimetric analysis of vitamin C were 7.0 x 10(-3) M cerium(IV), 0.455 M sulfuric acid and 28.9 microL s-1 flow rate. A linear calibration plot for the determination of vitamin C was obtained in the concentration range between 30 to 200 ppm. The method was applied to the determination of vitamin C in pharmaceutical preparations and no excipient was found to pose any interference, thus rendering the method suitable for the determination of the drug in pharmaceutical preparations. The SIA method is found to be accurate when the results were statistically compared with the results obtained by the BP standard method. The SIA method is superior when compared to the conventional titration method, the BP standard method and previous methods with respect to precision and automation in solution handling.

Rapid inexpensive assay method for verapamil by spectrophotometric sequential injection analysis.

Sequential injection analysis (SIA) technique with a miniaturized fibre optic spectrophotometry was exploited to optimize and validate a new method for the assay of verapamil in pharmaceutical formulations. The reduction of acidified permanganate by verapamil was spectrophotometrically detected at 546 nm. The 2(3) full-factorial design was adopted for screening the effect of conditions controlling the proposed method, and accordingly for the purpose of optimization. The remarkable advantages of the method are high rapidity (sample frequency was 10.6 samples/h), saving in reagents and sample (total consumed volume was 190 µl) and better safety for the environment (total waste production volume was 2140 µl). Additionally, the method was selective in the presence of excipients usually found in tablet and injection formulations. The average of recovery in synthetic samples as well as dosage forms was 98.8-103.0%. The obtained results were realized by the British Pharmacopoeia method and comparable results were obtained.

Voltammetric determination of josamycin (a macrolide antibiotic) in dosage forms and spiked human urine.

The voltammetric behaviour of josamycin (a macrolide antibiotic) has been studied using direct current (DC(t)) alternating current (AC(t)) and differential pulse polarography (DPP). In Britton-Robinson buffers, josamycin developed cathodic waves over the pH range 7-12. At pH 10, a well-defined cathodic wave with diffusion current constant of 1.06 +/- 0.19 (n = 5) was obtained. The wave was characterized as being diffusion-controlled; and partially affected by adsorption phenomenon. The current-concentrations plots are rectilinear over the range 10-60 and 6-50 microg/ml using DC(t) mode and DPP mode, respectively. The minimum detectability limit was 1.2 microg/ml (1.9 x 10(-6) M) adopting the DPP mode. A method was proposed for the determination of josamycin in its tablets adopting both DC(t) and DPP modes. The results obtained were in good agreement with those given by the manufacturer. The method was extended to the in-vitro determination of the drug in spiked human urine; the % recovery was 98.06 +/- 1.76% (n = 5). The number of electrons involved in the reduction process was accomplished and a proposal of the electrode reaction was presented.

Photodegradation Studies on Chloroquine Phosphate by High-Performance Liquid Chromatography

A method based on high-performance liquid chromatography (HPLC) was developed to study degraded chloroquine samples produced after exposure to sunlight in the Sudan. The method was also used to investigate chloroquine photodegradation after irradiation by UV and sunlight at ambient temperature. The study showed that the photodecomposition of chloroquine was pH and solvent dependent. Moreover, the extent of reaction was found to increase in the absence of oxygen. At pH 8, where the reaction rate was high, the photodecomposition was found to follow pseudo-first-order reaction kinetics. The HPLC method developed was also employed to analyse chloroquine and its degradation products in two commercially available brands of chloroquine injections which had been stored under local conditions in the Sudan. A number of degradation products were separated and examined by photodiode array spectroscopy and preparative TLC.

A study of chloroquine and desethylchloroquine plasma levels in patients infected with sensitive and resistant malaria parasites.

This study was carried out on 63 patients in the town of Gadaref in eastern Sudan; each patient was given the standard therapeutic dose of chloroquine (CQ). Plasma levels of chloroquine and its major metabolite desethylchloroquine (DCQ) were measured by means of a high-performance liquid chromatographic method (HPLC) in patients infected with sensitive (sensitive group) and resistant (resistant groups) strains of Plasmodium falciparum. The ratios of chloroquine to desethylchloroquine (CQ/DCQ) in different groups were calculated and the results obtained were compared and correlated with the degree of parasitaemia. The statistical analysis of the results showed that the plasma content of CQ and the CQ/DCQ ratio in the majority of the patients fall within the normal mode of distribution. A small group of patients showed a deviation from the normal mode by having a rather high CQ plasma level and a high ratio of CQ/DCQ. The mean plasma levels of CQ and the CQ/DCQ ratio in the sensitive group was found to be higher than that in the resistant groups. However, these differences were found to be not significant. Correlation tests showed that the levels of CQ and the CQ/DCQ ratios increase with the increase of the degree of parasitaemia in the sensitive group but decrease with the increase of parasitaemia in resistant groups.

Studies on the photochemical decomposition of metronidazole

Abstract The photodecomposition kinetics of the antiprotozoal drug, metronidazole, in different solvents and at different pH values, temperatures and drug concentrations has been investigated using sunlight and a photochemical reactor. The drug in the presence of its decomposition products was analyzed using different Chromatographic and spectroscopic techniques. The photodecomposition of the drug was found to follow pseudo-first-order kinetics.

Determination of chloroquine and its decomposition products in various brands of different dosage forms by liquid chromatography.

Various commercial preparations of chloroquine dosage forms have been examined both by thin-layer chromatography (TLC) and liquid chromatography (LC). TLC showed that all these preparations yielded more than one spot, indicating possible degradation. An LC method has been adapted for the determination of chloroquine in these drug formulations. The standard calibration curve was linear over the concentration range 1-6 micrograms ml-1. Chloroquine was assayed in various brands of different forms (ampoules, tablets and syrups). However, it was observed, for some samples, that the bands obtained were rather broad, showing shoulders or peak splitting, indicating the presence of other compounds coeluting with chloroquine. The utility of this method for the quality control of this major drug is assessed in the context of the need to carefully monitor drug purity in a tropical climate, particularly in situations where there may be doubt about the quality of the primary manufacturer.

Effects of alkali and simulated gastric and intestinal fluids on danazol stability.

The degradation kinetics of methanolic solution of danazol (0.020% w/v) in aqueous buffers and sodium hydroxide was investigated using stability-indicating HPLC method. The drug degrades in alkaline medium through a base-catalysed proton abstraction rather than via an oxidative mechanism involving oxygen species. The degradation followed pseudo-first-order kinetics. The rates pH-profile exhibited specific base catalysis. The stability of the drug was found to be dependent on pH, buffer concentration, buffer species (acetate, borate, phosphate) and temperature. The ionic strength did not affect the stability of the drug. The energy of activation according to Arrhenius plot was estimated to be 22.62 kcal mol(-1) at pH 12 and temperatures between 30 and 60 degrees C. The effect of simulated gastric and intestinal fluids on the drug stability was also investigated. Two major hydrolytic degradation products were separated and identified by IR, NMR and mass spectrometry and the degradative pathway suggested.

PHOTODEGRADATION KINETIC STUDIES AND STABILITY-INDICATING ASSAY OF DILOXANIDE FUROATE IN DOSAGE FORMS USING HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY

ABSTRACT The effect of different conditions on the photostability of diloxanide furoate (DF) was investigated. To perform stability studies on DF, a specific stability-indicating high-performance liquid chromatographic (HPLC) method was established using an ultraviolet detector set at 258 nm. The accuracy, precision, and reliability of the method for the assay of DF in its tablets dosage form were established. Assay results were within RSD values less than 2%. The stability-indicating power of the HPLC method was validated by UV-degraded DF solution in a mixture of acetonitrile:water (55 : 45 v/v) contained in quartz cells and glass bottles. The resultant chromatogram indicated that the degradation products were well separated from the parent drug. Photostability of DF was studied under different light exposures, i.e., UV-irradiation, room artificial light, and sunlight. Using the HPLC method, the photodegradation kinetics of the drug was studied in both a quartz cell and glass bottle. In both cases the photodegradation process followed first-order kinetics. The effects of different solvents on the UV-irradiation of DF are also reported. One of the three major degradation products observed was identified.

Stability‐Indicating HPLC Method for the Determination of Methicillin in Vials and Biological Fluids with Fluorometric Detection

Abstract A simple, stability‐indicating liquid chromatographic method has been developed for the determination of methicillin sodium in the presence of its acid and alkaline‐induced degradation products. A µBondapak–C18 column was used with a mobile phase composed of acetonitrile/2% v/v acetic anhydride (55:45 v/v) at a flow rate of 1.8 mL/min. The detection was accomplished fluorometrically using an excitation wavelength of 280 nm and emission wavelength of 360 nm. The peak area versus concentration plot was linear over the range 1–10 µg/mL with a limit of detection of 0.1 µg/mL (2.38×10−7 M). Between‐day and within‐day relative standard deviations were lower than 2%. The proposed method was successfully applied to the in‐vitro determination of methicillin sodium in bulk material, dosage form, spiked urine, and spiked plasma, with minor modification of the mobile phase ratio in the case of spiked urine and plasma. The % recovery from human plasma (n=9) was 99.04±1.88 and from urine (n=8) was 99.3 6±1.77.