| Abstract: |
In this thesis, two polyhydroxy phenolic reagents (hematoxylin and quercetin) are utilized for the determination of some P-Adrenergic blocking agents in pure as well as pharmaceutical preparations. For this purpose, two methods are developed. In the two methods both reagents are oxidized, hematoxylin is autoxidized by dissolved oxygen to give the highly coloured compound, while quercetin is oxidized by NBS before its reaction with studied drugs and extraction with the organic solvent.The first proposed method is a simple selective and sensitive spectrophotometric method for the determination of eight p-adrenergic blocking drugs having secondary amine moiety as a basic center. The investigated drugs are acebutolol hydrochloride, atenolol, metoprolol tartarate, nadolol, oxprenolol hydrochloride, pindolol, propranolol hydrochloride and timolol maleate. The method involves the reaction of the free bases of these drugs in aqueous solutions with hematoxylin reagent to form a highly coloured hematein (oxidized hematoxylin) measured at 558 nm. The reaction could be explained as the free bases of the drugs in aqueous solutions enhance both the autoxidation of hematoxylin and the ionization of the oxidized product (hematein) to give a reddish violet chromogen (hematein mono-anion). Factors affecting absorption intensity of the formed chromogen are studied. Thus the optimal concentration of hematoxylin reagent is chosen as 0.5 ml of 4.0 x 10’3 M solution. Keeping the reaction mixture at room temperature for 30 minutes is found to give the maximum intensityof the chromogen. The best solvent is found to be water. Moiar ratio of the reaction is determined and found to be 1:1 (hematoxylin : drug).Beer’s law is obeyed in the range of 1-12 jig/ml, with limit of detection of 0.24-0.64 j^g/ml for the investigated drugs. Also, precision and other quantitative parameters are determined and calculated. The method is applied for the determination of the studied drugs in tablets or eye DROPs. Results are in good comparison with those obtained by the corresponding official or reported methods.The second method is a simple, selective and sensitive extractive spectrophotometric assay for the determination of six P-adrenergic blocking drugs having secondary amine moiety. The studied drugs are acebutolol hydrochloride, metoprolol tartarate, oxprenolol hydrochloride, pindoloi, propranolol hydrochloride and timolol maleate. The method is based on the formation of an ion pair complex between the studied drugs and the oxidized quercetin, which is extracted with methylene chloride at pH 4.0 and at room temperature. The absorbances of the extracted coloured complexes are measured in the range of 526-533 nm against a reagent blank.NBS (N-bromosuccinimide) is chosen in the present investigation for the oxidation of quercetin. It is safe, stable, moderately effective oxidizing agent and its solutions in the concentration range of 2-20 x 10’3 M are colourless.Regarding the optimization of variables ; quercetin optimal concentration is found to be 6 x 10’3 M (0.5 ml) methanolic solution. A concentration of 8.0 x 10”3 M (1.0 ml) aqueous solution of N-bromosuccinimide is chosen for proper ion pair formation. Optimum pH value of the aqueous solution is 3.5-4.5. Ion pair complex developing time and stability are studied as well as the time of shaking with the organic solvents. Also the best order of mixing of the reaction components is investigated. With respect to the quantitative extraction of the ion pair complex, mehtylene chloride is recommended. Suitable solvent volume is determined.Beer’s law is obeyed for the studied drugs in the concentration range of 2-50 /^g/ml, with limit of detection of 0.23-2.95 ng/ml. There is a good correlation between the molar absorptivity of the formed ion pair complex and the partition coefficient of the studied drugs. Nadolol and atenolol fail to react with the oxidized quercetin, that may be due to their low lipid solubility. Also, it is found that the extraction efficiency increases as the value of the dielectric constant of the extracting solvent increases.other quantitative parameters are determined. The method is successfully applied for the analysis of the studied drugs both in the pure and in commercial dosage forms (tablets or eye DROPs). Results are in good comparison with those obtained by the corresponding official or reported methods.In most of the reported ion pair procedures, the absorption of the formed complex were measured nearly at 400 nm (i.e. near to the UV region). Also the sensitivity of the published procedures are lower than or similar to the proposed procedure, sometimes they expended longer time.The previous reported ion pair methods are usually utilized for the determination of a single compound but the proposed procedure is considered to be a general selective method for the determination of the basic compounds that have a relatively high partition coefficient (Table 4 page 6).It was noticed that, the presence of common tablet excipients have no significant effect in the proposed methods. The mean percentage recoveries are found to be 100.29 % ± 1.65 and 99.79 ± 0.48 for method (A) and (B) respectively.Hydrochlorothiazide present in some dosage forms does not interfere with the analysis of the studied drugs using method B, but a considerable interference is observed in method A. However, the presence of dihydralazine sulphate produces a significant interference in the analysis using both methods.
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