الفهرس 
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Abstract
The compounds investigated through out this work were determined in pharmaceutical preparations and human biological fluids as urine and breast milk. These compounds include flavoxate hydrochloride (FX) and its metabolite 3-methyl flavone ــ8 ــcarboxylic acid (MFA), atenolol (AT), chlorthalidone (CT), vincamine (VN), piracetam (PC), diflunisal (DF), naproxen (NX), dextromethorphane hydrobromide (DX), phenylephrine hydrochloride (PH), carbinoxamine maleate (CX), phenylpropanolamine (PN), methylparaben (MP), propylparaben (PP), and midodrine hydrochloride (MD).
The thesis consists of five chapters.
Chapter 1
Includes general introduction about the pharmacological effect of these compounds, their structures and solubility in different solvents.
Chapter 2
In this chapter, Liquid chromatographic method was presented for the determination of FX and its hydrolysis product. The method was based on high performance liquid chromatographic (HPLC) separation of FX from its hydrolysis product on CN column using a mobile phase consisting of acetonitrile - 12 mM ammonium acetate (45: 55, v/v, pH 4.0) with UV detection at 220 nm and flow rate of 1.5 ml min-1. The proposed HPLC method for determination of FX was utilized to investigate the kinetics of acidic hydrolytic process at different temperatures, and to calculate its activation energy. In addition, the proposed HPLC method was used for pH-rate profile study of hydrolysis of FX in Britton-Robinson buffer solutions.
Chapter 3
Divided into:
A- General introduction about drug analysis in biological fluids such as urine and human breast milk and how we could remove the interference of proteins and fatty acids in human breast milk.
B- High performance liquid chromatographic (HPLC) method was presented for the determination of MFA as the main active metabolite of FX in human urine. The proposed method was based on using CN column with mobile phase consisting of acetonitrile-12 mM ammonium acetate (40: 60, v/v) and adjusted to apparent pH 4.0 with flow rate of 1.5 ml min-1. Quantitation was achieved with UV detection at 220 nm. The proposed method was utilized to the determination of dissolution rate for tablets containing FX. The urinary excretion pattern as the cumulative amounts excreted have been calculated using the proposed method.
C- High-performance liquid chromatographic method was optimized and validated for the determination of AT and CT in breast milk. The milk samples were extracted and purified using acetonitrile and phosphoric acid for precipitation of proteins then removal of acetonitrile and milk fats by extraction with methylene chloride. The proposed method was applied after extraction procedure using CN column with mobile phase consisting of acetonitrile-water (35: 65, v/v) and adjusted to pH 4.0 with flow rate of 1.0 ml min-1. Quantitation was achieved with UV detection at 225 nm using guaifenesin as internal standard. The effectiveness of protein precipitants other than phosphoric acid was investigated; also the clean up procedure by liquid - liquid extraction using methylene chloride was investigated. The method was validated over the range of 0.3-20 µg ml-1 for AT and 0.25-5 µg ml-1 for CT.
Chapter 4
Divided into:
A- General introduction about the use of chemometric- assisted spectrophotometric methods in the analysis of multicomponent pharmaceutical preparations. The advantages and disadvantage of each method are reported.
B- Four methods were applied for the analysis of two sustained release mixtures containing DX, CX, with either PH in pharmaceutical capsules (Mix1) or PN, MP, and PP which bonded as drug base to ion exchange resin in pharmaceutical syrup (Mix 2). In the first method, liquid chromatography was used for their simultaneous determination using CN column with a mobile phase consisting of acetonitrile – 12 mM ammonium acetate, in ratio of (60: 40, v/v, pH 6.0) for mix 1, and (45:55, v/v, pH 6.0) for mix 2, with flow rate of 2 ml min-1 and UV detection at 214 nm. Also, three chemometric methods, classical least squares, principal component regression, and partial least squares were used. The calibration of CLS, PLS-1 and PCR models were evaluated by internal validation (prediction of compounds in its own designed training set of calibration), by cross-validation (obtaining statistical parameters that show the efficiency for a calibration fit model) and by external validation over synthetic and pharmaceutical preparation. The results of CLS, PLS-1 and PCR methods were compared with the HPLC method and a good agreement was found.
C- Three methods were applied for the analysis of two binary mixtures containing VN and PC in pharmaceutical capsules (Mix 1) or DF and NX in pharmaceutical tablets and suppositories (Mix 2). Numerical spectrophotometric methods as partial least squares PLS-1, and principal component regression PCR applied to the UV absorption spectra of the two binary mixtures were used for the determination of their components without any separation steps. In addition, HPLC method was used for their simultaneous determination using an ODS column with a mobile phase consisting of acetonitrile – 20mM potassium dihydrogen phosphate ــ diethylamine, (40:60:0.2, v/v, pH 3.0), and ultraviolet (UV) detection at 220 nm for mix 1, and mobile phase consisting of acetonitrile – 20mM potassium dihydrogen phosphate ــ diethylamine, (65:35:0.2, v/v, pH 3.0) with UV detection at 230 nm for mixture 2. The developed methods are simple, precise, rapid and selective.
Chapter 5
A simple and fast spectrophotometric method has been developed for the determination of MD in pure form and in pharmaceutical formulations. The method is based on the reaction of the primary amino group of the drug with ninhydrin in methanol producing a Ruhemann purple coloured complex which absorbs maximally at 576 nm. The effects of different variables such as reagent concentration, reaction time, reaction temperature, and Ruhemann purple color stability period, were investigated to optimize the procedure. The proposed method has been applied successfully to the analysis of the bulk drug and its pharmaceutical tablets and DROPs. No