الفهرس 
Cyclic voltammetryOnly 14 pages are availabe for public view
 |  | from | 328 |  |  |
| | | from | 328 | | |
Abstract
Isoniazid, Ranitidine, Ketoprofen, Captopril, Terfenadine, Praziquentel and Loratadine are pharmaceutical compounds of great biological importance. In this thesis, it is aimed to study the electrochemical behaviour of these compounds in buffer solutions of different pH values to elucidate their electrode reaction mechanisms. It is aimed also to optimize the experimental and instrumental conditions for the trace quantitative determination of these compounds in their dosage forms and in human serum using cathodic adsorptive stripping voltammetry technique. The thesis comprises of three main chapters: Chapter I : It presents a general introduction of the electrochemical analysis of pharmaceutical compounds and short notes on the principles of the different electrochemical techniques used in the present study. Also, it presents a literature survey on the pervious electrochemical and analytical studies of the investigated pharmaceutical compounds. Chapter II: It contains the experimental part. It describes the materials, preparation of the various solutions used in the present study. This chapter contains also description of the instrumentations used in the present measurements such as dc-polarography, cyclic voltammetry, coulometry, differential pulse polarography and cathodic adsorptive stripping voltammetry. Chapter 111: It includes the obtained results and discussion of all the electrochemical data of the different investigated pharmaceutical compounds. This chapter contains seven parts: 1-Isoniazid: The electrochemical behaviour and electroanalytical determination of Isoniazid in its dosage forms and human serum are studied in B.R.buffer solution of different pH values. It reduced through two polarographic waves of unequal height within the pH range 1.9-8.3. The fxst wave corresponds to 2-electrons saturation of N=C of the pyridine ring, while the second wave corresponds to the saturation of the C=N center and the reductive splitting of N-N bond of the hydrazo group via the consumption of four electrons in one step. At pH > 8 the polarograms exhibit one reduction wave corresponds to the saturation of both the N=C of the pyridine ring and C=N center. The half-wave potential is pH dependent, being shifted to more negative value with increasing pH. The total wave height is pH dependent within the pH’s < 7, it decreases in the alkaline medium. The logarithmic analysis of the polarographic waves indicated that the reduction process proceeds irreversibly. The effect of mercury height on il indicates that the electrode process is mainly controlled by difision with partial adsorption contribution. The most probable values of the (a) parameter denote that the ratio (ZH+ Ina) = 0.5. Thus, the number of protons involved in the rate determining step is half that of the consumed electrons. The cyclic voltammetric behaviour of Isoniazid is investigated at the hanging mercury DROP electrode (HMDE), in Britton - Robinson buffer solution of pH (2-11). The obtained voltammograms display two cathodic peaks in acidic and neutral media, while in alkaline medium they exhibit only one cathodic peak. The peak potential (q) is shifted to more negative value with rise of pH. On plotting i, versus square root of the scan rate (dv), a linear relation deviating from the origin is obtained confirming that the reduction process of Isoniazid is controlled mainly by difision with partial adsorption contribution. Also, the kinetic parameters of the electrode reaction are discussed and calculated. The greatest advantage of the determination of Isoniazid by adsorptive stripping voltammetry is its high sensitivity. Accumulation of Isoniazid was found to be optimized in B.R.buffer solution of pH=6 under the experimental and instrumental conditions: deposition potential = -0.4V; accumulation time= 240 s; scan rate = 10 mV/s and pulse height = 100 mV. The method was applied successfully for trace quantitative determination of Isoniazid in its dosage forms and human serum. The detection limit of Isoniazid in its dosage forms and in human serum is found to equal 5.04~1 0-8 M and 5.37 1x1 o-~M, respectively. 2-Ranitidine: The electrochemical behaviour and electroanalytical determination of Ranitidine in its dosage forms and human serum are studied. The polarographic reduction of Ranitidine is studied in the Britton-Robinson buffer solution of pH (2 - 11). At pH < 3, the polarograms exhibit two waves; the first wave decreased markedly while the second wave increases at the expense of the first one up to pH 5.1, while the total limiting current is almost pH-independent. At pH 6-1 1, the polarograms exhibit one 6-electrons wave due to the reduction of the nitro group to hydroxyl amine stage via the consumption of 4-electrons and saturation of C=C center via two electron transfer. The half-wave potential is pH- dependent, it shifted to more negative value with increasing pH denoting the participation of H+ ion in the electrode reaction. Effect of mercury height on il indicates that the electrode process is mainly controlled by diffusion with partial adsorption iii contribution. The most probable values of the (a) parameter denote that the ratio (ZH+ Ina) = 0.5 and the number of protons involved in the rate- determining step is equal to unity. The logarithmic analysis of the polarographic waves indicated that the reduction process proceeds irreversibly. Also, the kinetic parameters of the electrode reaction are evaluated and discussed. The cyclic voltammetric behaviour of Ranitidine is investigated at the hanging mercury DROP electrode (HMDE), in Britton-Robinson buffer solution of pH (2- 11). The obtained voltammograms display two cathodic peaks in acidic medium, while in neutral and alkaline media they exhibit one cathodic peak. The peak potential 6) shifts to more negative value with rise of pH. The plot of E, versus In (v) gives a linear correlation with slope values proportional to (an,). On plotting i, versus square root of the scan rate (dv), a linear relation deviating from the origin is obtained confirming that the electrode process of Ranitidine is controlled mainly by diffusion with some adsorption contribution. Accumulation of Ranitidine at the mercury electrode surface was found to be optimized in B.R.buffer solution of pH=l 1 under the experimental and instrumental conditions: deposition potential= -0.7V; accumulation time= 120 s; scan rate = 5 mV/s and pulse height = 100 mV. The method was applied successfully for analysis of dosage forms and human serum. The detection limit of Ranitidine determination in its dosage forms and human serum is found to equal 2.19~10’~ M and 8.4x10-’~, respectively. 3-Keto~rofen: The electrochemical behaviour and electroanalytical determination of Ketoprofen in its dosage form and human serum are studied. The polarographic reduction of Ketoprofen is studied in the Britton- Robinson buffer solution of pH (2 - 11). In acidic medium (pH 2-3) the polarogram consists of two waves of almost equal height. These two waves merge together in the pH range 4-6. At pH values 6-8 the wave splits again into two waves of unequal heights. The height of the first wave decreases with increasing pH while the second wave increases. The two waves are transformed again to a single one at higher pH values (9-1 1) which may be due to the presence of the investigated compound in its anionic form only. The half-wave potential of the less negative wave depends on pH, whereas that of the more negative one is almost pH-independent. This behaviour may be attributed to the fast acidbase equilibrium preceding the uptake of the fust electron but does not involve proton transfer between the transfer of the first and second electron. Effect of mercury height confirmed that the electrode process is controlled by difision with adsorption contribution. The most probable value of (a) parameter denote that the ratio (zH+/n,) = 1 .O. The cyclic voltammetric behaviour of Ketoprofen is investigated at the hanging mercury DROP electrode (HMDE), in Britton - Robinson buffer solution of pH (2- 11). Each of the obtained voltammograms displays one or two cathodic peaks. The irreversible nature of the reduction process is confirmed by the shift of the peak potential (E,) to more negative values with increasing the scan rate, On plotting i, versus square root of the scan rate (dv), a linear correlation is obtained which deviates from the origin confirming that the electrode process of Ketoprofen is controlled by difision with partial adsorption contribution. The kinetic parameters of the electrode reaction is calculated and discussed. Accumulation of Ketoprofen at the electrode surface was found to be optimized in acetate buffer solution of pH=5.6 under the experimental and instrumental conditions: deposition potential= -0.6V; accumulation time = 30 s; scan rate= 5 mV/s and pulse height = 100 mV. The method was applied successfully for analysis of dosage forms and human serum. The detection limit of Ketoprofen in its dosage form is lxl@’M and 1 .1 x1 O-~M in human serum.