Determination Of Some Pharamaceutical Mixture Samples By Volatmmetry With The Aid Of Chemometrics

This thesis is divided into five parts. It mainly researches the simultaneouse determination of pharmaceutical samples in complicated systems with the aid of chemometrics.Part one: In this part, it is described and reviewed the application of electroanalytical chemistry in the determination of pharmaceutical analysis in the last ten years. The potentiometry, the voltammetry and the polarography methods have been described in details. According to the features of the voltammetric method, such as selective, sensitive, rapid and inexpensive instruments, and the powerful resolution capability of chemometrics approaches.Part two:The voltammetric behaviour of three 5-nitroimidazoles, metronidazole, tinidazole and ornidazole, was investigated, and a method was developed for the simultaneous determination of these compounds, based on their reduction at a hanging mercury drop electrode (HMDE) in pH 8.95 buffer with differential pulse voltammetric (DPV) approach. Well defined voltammetric waves with peak potentials of-692.-640 and-652 mV were observed for these compounds, respectively. It is difficult to determine them individually from their mixtures without preseparation. for their voltammetric peaks overlapped seriously, so the chemometrics were used to resolve the overlapped voltammogram and quantify the mixtures. The proposed method was successfully applied to the determination of three 5-nitroimidazoles in milk and honey samples.Part three:In chapter three, the electrochemical behavior and the contemporary determination method in the metabolic blood of three kinds of nucleoside analogues as antivirus named Aciclovir Valaciclovir and Famciclovir, on the ethylenediamine modified glassy carbon electrode were investigated by differential pulse voltammetry. In the pH=4.56 Britton-Robinson buffer solution, Aciclovir Valaciclovir and Famciclovir had a sensitive irreversible oxidation peak on the ethylenediamine modified glassy carbon electrode. The peak potentials of the three medicines were 1.096,1.074 and 1.200 V respectively. Under the optimal condition, the peak current of Aciclovir was linear with its concentration in the range of 0.10～1.40μg mL-1, the concentration range of Valaciclovir was 0.03～0.54μg mL-1 and the Famciclovir was linear with its concentration in the range of 0.05～0.90μg mL-1. The detection limits were 77,30, and 40 ng ng mL-1 relatively. The paper inducted chemometrics to determine the admixture of the three medicines. The proposed procedure was applied for the quantification of the three nucleoside analogues as antivirus in rabbit serum samples and the results were compared well with HPLC method.Part four: Three structurally similar catecholamines, adrenaline (AA). dopamine (DA) and noradrenaline (NA), which are neurotransmitters well known for their treatment of neural disorders and many other diseases, were investigated at a glassy carbon electrode (GCE) with the use of differential pulse stripping voltammetry (DPSV). The aim was to develop a simple, rapid and cost effective method of simultaneous analysis of these three substances in typical samples such as Inuman urine. Each analyte showed typical reversible redox behaviour with the use of cyclic voltammetry in aqueous medium in the pH range of 4.0～7.9, and composite voltammograms of the three analytes were found to consist of three significantly overlapping peaks corresponding to the three individual substances. Thus, two- and threeway multi-variate data analysis methods were investigated. These included unfolding methods such as-partial least squares (UPLS), principal component regression (UPCR) and radial basis functionartificial neural networks (URBF-ANN), as well as trilinear models, such as parallel factor analysis (PARAFAC) and N-way PLS (NPLS). The results were compared with those obtained from two-way voltammetric data matrix with the use of conventional models, PLS, PCR and RBF-ANN. It was found that most of the three-way models, such as PARAFAC and UPLS, performed somewhat better than others on the basis of the %RPET (5.6～5.9) and mean % Recovery (94～102). The proposed methods were then applied for the determination of human urine samples spiked with the three catecholamines, and'the results were satisfactory.Part five:A method, using differential pulse stripping voltammetry (DPSV), for the simultaneous determination of Pyrazinamide(PZA), Isoniazid(INH), Rifapentine(RFP) and Rifampin(RIF) in urine samples is reported. All four compounds produce, at mercury electrode (HMDE), an electrochemical signal due to an oxidation-reductive process. The electrochemical approach shows a very high overlap degree for the four voltammograms. Second-order multivariate calibration has been tested to solve the mixture of the four compounds. The second-order assayed methods were parallel factor analysis (PARAFAC), unfolded partial least squares (U-PLS) and multidimensional partial least squares (N-PLS). N-PLS model was stated as the best second-order algorithm for the simultaneous determination of these four compounds. The detection limits were 0.1719μg mL-1 for PZA; 0.1748μg mL-1 for INH 0.0316μg mL-1 for RFP and 0.1228μg mL-1 for RIF.