الفهرس يوجد فقط 14 صفحة متاحة للعرض العام
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المستخلص
This thesis is concerned with the analysis of certain macrolide antibiotics namely; azithromycin dihydrate, erythromycin ethylsuccinate, clarithromycin, and roxithromycin. The thesis comprises two parts in addition to general introduction about macrolide antibiotics especially the selected drugs and the different official and reported methods described for the assay of these drugs.
Part 1:
Includes spectrophotometric methods for the determination of the studied macrolides, and it is comprised of two chapters.
Chapter 1:
Includes a simple, rapid, accurate and sensitive spectrophotometric method which is developed for the determination of the studied macrolides using concentrated sulphuric acid that form a coloured product. The absorbance was measured at max. 485 nm for all studied macrolides. Investigations were carried out to study all variables and the effects of commonly encountered excipients. A validation study for the proposed procedure according to USP 2002 was performed. Beer’s law was obeyed for all of the studied macrolides in the concentration range of 5 – 60 µg ml-1. The detection limit range was 0.708 – 1.041 µg ml-1, while the quantitation limit range was 2.360 – 3.469 µg ml-1. The method was successfully applied for the analysis of the studied macrolides in pure and pharmaceutical dosage forms. Results were compared with those obtained from the reported methods. The t- and F- values were calculated and compared with the theoretical values indicating high accuracy and good precision of the proposed method.
Chapter II:
This chapter involves charge transfer complexation reactions using - and -acceptors, and consists of two sections.
(A) Using - acceptor as iodine.
(B) Using -acceptors as; 2,3-dichloro-5,6-dicyano-1,4-benzoquinone(DDQ),
7,7,8,8-teracyanoquinondimethane (TCNQ),and p-chloranilic acid (p-CA)
These methods are based on the interaction between the tertiary amine group in desosamine sugar moiety and/or macrocyclic lactone ring of the studied macrolides as n-electron donor and - and -acceptors. The produced charge transfer complexes were measured at 290, 363 in dichloromethane for iodine, and at 460, 843, and 520 nm in methanol, acetonitrile and acetonitrile for DDQ, TCNQ, and p-CA respectively. Investigations were carried out to study all variables and the effects of commonly encountered excipients. A validation study for the proposed procedure according to USP 2002 was also carried out. Beer’s Lambert law was obeyed for all of the studied macrolides by the four reagents at their corresponding maxima over a wide range of concentrations. The molar ratio of iodine, DDQ, TCNQ, and p-CA to each of the studied drugs was 1:1 except for azithromycin was 2:1. The method was successfully applied for the analysis of the studied macrolides in pure and pharmaceutical dosage forms. Results were compared with those obtained from the reported methods. The t- and F- values were calculated and compared with the theoretical values indicating high accuracy and good precision of the proposed charge transfer methods.
Part 2:
In this part the studied macrolides were analyzed by a simple spectrofluorimetric method. The method is based on the condensation of malonic acid and acetic anhydride under the catalytic effect of the tertiary amine groups of the studied macrolides. The relative fluorescence intensity of the condensation product was measured at exc.397 nm, em.452 nm for azithromycin dihydrate, and at exc.392 nm, em.445 nm for clarithromycin, erythromycin ethylsuccinate, and roxithromycin. All variables affecting the reaction conditions were studied. The effects of potential interference due to common excipients as; (starch, lactose, sucrose, glucose, gum acacia, and magnesium stearate) as well as trimethoprim and sulphisoxazole acetyl formulated in primomycin capsules ans pediazole oral suspension, respectively were studied. A validation study of the proposed method was carried out according to USP 2002. The linearity ranges were 3 – 80 ng ml-1 for all the cited macrolides. The limit of detection range was 0.742 – 1.205 ng ml-1, while the limit of quantitation range was 2.474 – 4.016 ng ml-1. The method was applied for the assay of the studied macrolides in pure, pharmaceutical dosage forms, and in spiked biological fluids. Results were compared with those obtained from the reported methods, where t- and F- values were calculated and compared with the theoretical values. They indicate high accuracy and good precision of the proposed method.
N.B. A part of this thesis has been puplished in Bulletin of the Faculty of Science, Assiut University , 31 (1), 2002.