الفهرس يوجد فقط 14 صفحة متاحة للعرض العام
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المستخلص
This thesis is concerned with the analysis of certain medicinally important thiol and thioamide compounds namely; acetylcysteine, captopril, thiopental sodium, tiopronin, carbimazole and propylthiouracil. Depending on the reducing properties of these compounds, different techniques (spectrophotometric and spectrofluorimetric) were used. The thesis comprises two parts in addition to introduction about the studied drugs and the different official and reported methods described for their analysis.
Part I:
This part includes spectrophotometric methods for the determination of the studied thiols and thioamides, and it is divided into three chapters.
Chapter 1:
Includes a simple, rapid and sensitive spectrophotometric method, which is developed for the determination of the studied drugs by reaction with oxidized diphenylamine (diphenylbenzidine). The method depended on the reducing properties of the studied drugs. By measuring the decrease in the absorption intensity of the violet color of diphenylbenzidine violet due to the presence of the studied drugs. The decrease in the absorption intensity was measured for all the studied drugs at 580 nm. A study for all variables was carried out to optimize the reaction conditions. A validation study for the proposed procedure according to USP 2002 was performed. Beers law was obeyed in the range of 0.4 - 70.0 ug/ml. The detection limits ranged from 0.10 - 4.49 ug/ml, while the quantitation limits ranged from 0.34 - 7.69 fig/ml. The method was successfully applied for the analysis of the studied drugs in pure and in pharmaceutical preparations
with good recoveries in the range of 97.98- 99.85 %. Results were compared with those obtained by pharmacopoeial or reported methods. The t-and F- values were calculated and compared with the theoretical values, which indicate high accuracy and precision of the proposed method.
Chapter 2:
This chapter involves the direct oxidation of the studied drugs using ammonium vanadate (V) solution. The procedure depends on measuring the absorption intensity of the produced vanadium (IV) at 750 nm. Investigations were carried out to study all variables affecting reaction conditions and a validation study for the proposed procedure according to USP 2002 was also performed. Beer s law was obeyed in the range of 8.5 -140.0 fig/ml. The detection limits range was 2.47 - 4.83 jig/ml, while the quantitation limits range was 8.42 - 16.10 |ig/ml. The method was successfully applied for the analysis of the studied drugs in pure and in pharmaceutical preparations with good recoveries in the range of 98.00-99.78 %. Results were compared with those obtained by pharmacopoeial or reported methods.
Chapter 3:
In this chapter the studied drugs were analyzed by a simple oxidation - reduction method. The method depends on the oxidation of the studied drugs with excess ammonium cerium (IV) sulfate. Followed by measuring the excess unreacted ammonium cerium (IV) sulfate, through reaction with p-DMAB into the corresponding p- dimethylaminobenzoquinone, which Bias a red color can be measured at 464 nm. The decrease in the absorption intensity at 464 nm caused by the presence of the investigated drugs is directly proportional to their concentration. Investigations were carried out ho study all variables and a validation study for the proposed procedure according to USP 2002 was also performed. Beer s law was obeyed in the
range of 1- 40 ug/ml. The detection limit ranged from 0.22 - 1.22 ug/ml, while the quantitation limit ranged from 0.73 - 4.06 jig/ml. The proposed method was successfully applied for the analysis of the studied drugs in pharmaceutical preparations with good recoveries in the range of 98.12-100.02 %. Results were compared with those obtained from pharmacopoeial or reported methods.
Part II:
In this part, the studied drugs were analyzed by a simple spectrofluorimetric method. The method is based on the oxidation of the studied drugs with ammonium cerium (IV) sulfate in presence of sulfuric acid and measuring the fluorescence of the produced Ce (III) at 355 nm (Excitation at 255 nm). All of the variables affecting the reaction condition were carefully studied. A validation study for the proposed procedure according to USP 2002 was also performed. The linearity ranged from 5 -200 ng/ml. The detection limit ranged from 1.25 - 4.78 ng/ml, while the quantitation limit ranged from 4.19 - 15.93 ng/ml. The proposed method was satisfactorily applied for the determination of the studied compounds in pure and in pharmaceutical preparations with good recoveries in the range of 98.76- 99.48 %. Results obtained were compared with those obtained from official and reported methods. Also the proposed method was successfully applied for the determination of the studied drugs in biological samples (human urine), it was found that, the percentage recoveries ranged from 97.35-99.60% with standard deviation less than
Chapter 1 of this thesis has been accepted for publishing in Bulletin of pharmacy, Assiut University, 28 (2) 2005, under the title of; Oxidized diphenylamine as a redox spectrophotometric reagent for the determination of some pharmaceutically important thiol and thioamide drugs.
Table 42: A comparison between all the proposed methods.
Method
Reaction Oxidation Linear
(nm) time, potential range
Temperature
LOD
-l___-l
LOQ 8, L.mole . cm
(min, °C)
I- Spectrophotometric methods +
A- Oxidized diphenylamine 580 5,60 0.76 (a) 0.4-70.0 0.10-2.31 0.34-7.69 2901-20445
B- Ammonium vanadate
750 15-25, 100 0.35 (a) 8.5-140.0 2.52-3.55 8.42-11.83 1256-2533
C- Ammonium cerium (IV) sulfate - p-DMAB
464
5,25 1.75 (b) 1.0-40.0 0.22-1.22 0.73-4.06 5434-20889
II- Spectrofluorimetric method ++
Ammonium cerium (IV) sulfate Xem 355 5, 25
Aex 255
1.44 (b) 5.0-200.0 1.02-4.78 3.40-15.93
All concentrations; (+) in p.g/ml, (++) in ng/ml.
a: Reference 182 b: Reference 188