Part 1.1: Determinations of captopril was made using a nanocomposite electrode modified with CuO nanoparticles (CuONPs) and multiwall carbon nanotube (MWCNT). The voltammetric results indicate that MWCNT can remarkably enhance electrocatalytic activity toward the oxidation of captopril in buffer solution. Characteristics of the electrochemical responses of the modified electrode toward captopril were investigated by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and chronoamperometry. The parameters of charge transfer coefficient (α), diffusion coefficient (D), electrode surface area (A), and catalytic rate constant (kh) were determined and the results were investigated. The electro catalytic oxidation current of captopril was found to have a linear relation to concentration over the range 4.6×10-7 M – 1×10-5 M (n=7) determined by the DPV method. The limit of detection at S/N ratio of 3 was 2.9×10-7 M (n=6) and the relative standard deviation was 4.4% at the 4×10−6M level (n=6). The prepared modified electrode has the advantages of high sensitivity and low detection limit in comparison with some reported methods and also simple preparation and regeneration of the electrode surface by polishing that enables acceptable reproducibility. The modified electrode can be applied to the determine of captopril in tablets and urine samples with satisfactory results.
Part 1.2: A simple and rapid square-wave adsorptive voltammetric (SWAV) method was developed for the determination of captopril (CAP) in pharmaceutical formulations. The proposed method was based on the electrochemical reduction of CAP at a thin mercury film electrode (TMFE). The preparation of the TMFE/Glassy carbon electrode is very simple, this electrode has a very good reproducibility, stability, and regenration of its surface is very easy. For many years mercury electrodes were the transducer of choice in voltammetry of trace analysis. However, because of the toxicity of mercury, alternative electrodes with a similar performance and lower toxicity are desired. One of the new classes of electrodes is thin film electrodes, especially TMFEs. This kind of electrode has the advantages of mercury electrode while a negligible amount of mercury is used. In this study, the TMFE in situ produced on glassy carbon electrode to the adsorptive voltammetric quantification of trace amount of CAP for the first time. The TMFE has been shown extremely useful for voltammetric measurements of CAP in µM level. Under optimized conditions, the SW adsorptive stripping voltammetric peak current showed a linear correlation on drug concentration over the range of 4.6–64.5 µM with a correlation coefficient of 0.992. The limit of detection at S/N ratio of 3 was 0.6 μM for CAP (n = 6) and the relative standard deviation for 23 μM of CAP (n=6) was 6.9%. The film electrode has the advantages of acceptable sensitivity, reproducibility, and simple preparation. The TMFE was applied to determine CAP in tablet samples with satisfactory results.
Part 2.1: In this research, we have developed a simple colorimetric method for detection of resorcinol (RE); the method is based on the reaction of RE with silver ions (oxidizing agent) in the presence of starch as a stabilizer and formation of silver nanoparticles (AgNPs). At nanometer dimensions the electron cloud can oscillate on the particle surfaces when dispersed in liquid media so these nanoparticles exhibit a strong UV-Vis extinction band. A UV-Vis spectrophotometer is used to monitor the changes of the localized surface plasmon resonance(LSPR) of AgNPs at a wavelength of 430 nm. There is a linear relationship between absorbance intensity of AgNPs and concentration of RE over the range of 4 μM to 11 μM at 430 nm. The detection limit was 4 μM. The proposed method has been successfully applied for the determination of RE in anti-acne solution and spiked shampoo samples.
Part 2.3: A colorimetric sensor for hydrazine with high selectivity and sensitivity by gold nanoparticles (AuNPs) within about 4–5 min at room temperature is presented. In this paper, the reduction of AuCl4− to gold nanoparticles by hydrazine compound produced very intense surface plasmon resonance peak of AuNPs. The formation of gold nanoparticles as a result of the redox reaction in water samples was identified by measuring the localized surface plasmon resonance (LSPR) absorption. The LSPR intensity displays a linear response with the hydrazine content over the range from 6.0 to 40.0 × 10−6M, with a detection limit of 1.1 × 10−6M. The relative standard deviation (R.S.D.) for determination of 10 × 10−6M and 28 × 10−6M of hydrazine was 3.2% and 0.68% (n = 6), respectively. The proposed method is convenient, low-cost and free of complex equipment, making it possible to successfully analyze hydrazine in industrial water samples (boiler and cooling water) and river water.
Part 2.4: A simple, inexpensive and fast colorimetric method was developed for the detection of hydralazine (HY), which is an antihypertensive drug. The method is based on the reaction of HY with ferric ions (as oxidizing agent) in the presence of ferricyanide ion and formation of prussian blue nanoparticles (KFe(III)[FeII(CN)6]). A UV-Vis spectrophotometer was used to monitor the changes of the absorption intensity of the prussian blue nanoparticles. These nanoparticles exhibited a strong UV-vis extinction band at 700 nm. Change in color of the solution, which is directly related to the HY concentration, could be easily observed with the naked eye in the presence of a sub-ppm level of HY. The effect of several reaction variables on the rate of the prussian blue nanoparticles formation was studied and optimized. A linear relationship between absorbance intensity of PBNPs and concentration of HY over a range of 0.4 μg mL-1 to 2.0 μg mL-1 with correlation coefficient (R2) of 0.9967 was observed; moreover, the detection limit was found to be 0.33 μg mL-1. The proposed method showed a good detection limit, and compared to other methods it is very fast, simple and inexpensive. Furthermore, the proposed method was successfully applied for the determination of HY concentration in pharmaceutical samples with satisfactory results.
Part 3.1: in this study, a hollow fiber liquid–liquid–liquid microextraction (HF-LLLME) technique for extracting lidocaine from human plasma, urine and injection vial samples is presented. It was combined with high performance liquid chromatography ultraviolet detection (HPLC/UV). In this experiment, lidocaine was successively extracted from a sample donor phase into several microliters of an organic phase and then from the organic phase into an aqueous extract acceptor phase. The following separation and quantitative analysis were performed using HPLC/UV at 205 nm detection wavelength. Extraction conditions such as selection of solvent, acceptor phase pH and donor phase pH, agitation rate, extraction time and salt addition effect were investigated and optimized. Under optimum conditions, a limit of detection (LOD) of 0.01 μg mL-1, a linear range of 0.05–2 μg mL-1 and a correlation of determination (R2) of 0.9994 were obtained. The intra-day relative standard deviation based on three replicate determinations in each day and three sucssessive days for 0.8 μg mL-1 was 8.2% and inter-day relative standard deviations (RSD %) based on five replicate measurements in one day for 0.8 μg mL-1and 0.08 μg mL-1were 2.01% and 6.90%, respectively. Extraction and determination of lidocaine in human plasma, urine and injection vial samples were successfully performed.
Part 3.2: A new and simple hollow fiber liquid-phase microextraction was used in conjunction with HPLC for the extraction and quantitative determination of nalidixic acid in human urine samples. The current study considers this technique as an alternative to the common methods of hollow fiber microextraction based on pH gradient and electromembrane extraction of nalidixic acid in human urine samples. In this research, the drug was extracted from the source phase (donor phase) into a modified organic phase with Aliquat 336 (hydrophobic ion-pair reagent) as a carrier able to impregnate pores of the hollow fiber. In this study, the effects of several factors were tested on the extraction efficiency of the drug. Under optimum conditions, the linearity of the method was observed over the range 0.05–2.0 µg. mL−1 with a correlation coefficient of R2=0.9967. Results of tests on the method determined a good sensitivity with a limit of detection of 0.009 µg. mL−1. The intra-day relative standard deviation (n=9) for 0.8 µg. mL-1 was 6.2%, and the inter-day relative standard deviation (n=5) for 0.8 µg. mL-1 was 5.6%. This new strategy was successfully applied to analyze a real urine sample with satisfactory results.