Development of electrochemical and stability-indicating chromatographic methods for determination of cefprozil

In this thesis, it is aimed to develop an electrochemical method for the determination of CFP and a stability indicating chromatographic analysis method for the determination of CFP's isomers. This study is the first voltammetric study describing determination of CFP. Firstly, the electrochemical behavior of CFP was examined separately over a pH range from 2,0 to 10,0 in BR , phosphate , acetate buffers and 0,1 M and 0,5 M sulfuric acid using cyclic voltammetry and differential pulse voltammetry. Experiments were performed in a wide scanning range (10-500 mVs-1) in pH 3 BR buffer, to examine the oxidation reaction of CFP. CFP was oxidized irreversibly and by diffusion-controlled at glassy carbon electrode. Quantification studies with differential pulse voltammetry. were carried out. The accuracy, precision, sensitivity, repeatability and reproducibility of the method was investigated statistically. A high performance liquid chromatography (HPLC) method, using paracetamol as the internal standard, was developed and validated for the determination of CFP' s diastereoisomers. Firstly, the best stationary phase for the separation of substances has been determined by testing various stationary phases. On the other hand, experimental conditions such as different moving phases, buffer solutions at different concentrations, pH, temperature, flow rate effects are also optimized. A good chromatographic separation was achieved using ACE 5 C8 (150 mm x 4,6 mm x 5 µm) column and acetonitrile: buffer solution (5 mM, ammonium acetate), 90:10 (v / v) mobile phase composition. The separation of CFP diastereomers was carried out at a flow rate of 1 mL min-1, 45°C, and a detection wavelength of 280 nm. Under these conditions, the retention time of cis-CFP, trans-CFP and PAR is 2,42 2,84 3,55, respectively. The HPLC method was validated according to the International Conference on Harmonization (ICH) guidelines and as a result of difficult degradation studies (oxidation, UV light, acid, base and temperature), the method was determined to have high selectivity for CFP. The proposed voltammetric and stability-indicating chromatographic methods have been successfully applied in pharmaceutical dosage forms. Thus, it has been shown that the analysis results are not affected by the excipients and its applicability to drug samples. Both methods was validated and their applicability for analysis from synthetic biological samples will be demonstrated. The developed methods are fast, selective, sensitive, reliable and environmentally friendly methods.