الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
This thesis comprises six main parts:
This part is an introduction reviewing the different natural and synthetic human sex hormones, their therapeutic uses and combinations in types of oral contraceptives.
This part is concerned with the different methods of drug analysis of human sex hormones. Special attention has been given to GC and GC-MS techniques and their applications to analysis of steroid hormones in bulk in pharmaceutical formulations as well as in biological fluids. respect, the most recent available publications were reviewed.
This part describes the experimental conditions for preparation of methoxime silylether derivatives of steroids. It also includes detailed prescription of all investigated steroids, reagents, as well as the different GC and GC-MS instruments conditions.
This thesis comprises six main parts:
This part is an introduction reviewing the different natural and synthetic human sex hormones, their therapeutic uses and combinations in types of oral contraceptives.
This part is concerned with the different methods of drug analysis of human sex hormones. Special attention has been given to GC and GC-MS techniques and their applications to analysis of steroid hormones in bulk powder, in pharmaceutical formulations as well as in biological fluids.
In this respect, the most recent available publications were reviewed.
PART I II
This part describes the experimental conditions for preparation of silylether and methoxime silylether derivatives of steroids. It also includes detailed prescription of all investigated steroids, reagents, solvents, solutions as well as the different GC and GC-MS instruments and their operating conditions.
PART IV
This part deals with the qualitative study of the GC and GC-MS properties of 22 different steroids in the form of their silylether deriivatives. New derivatives of seventeen 17 ~e~~. hydroxysteroids were prepared using the silylating reagents DMESI and DMiPSI. The GC behavvior of the steroid silylethers has been studied on both packed column
(1% OV-1) using isothermal oven temperature and capillary column (25 m CPSil 5 CB) using oven temperature programming. Typical GC traces and mass spectra line diagrams of steroid DMES and DMiPS ethers are presented in a comparative way so as to visualize spectra of structurally related compounds and to assist identification of fragmentation pattern. The study revealed good GC and GC-MS properties of both DMES and DMiPS ether derivatives of all the 22 studied hydroxysteroids.
PART V
This part includes the GC and GC-MS assay results and discussion of five different steroid hormones. Ethinyloestradiol, mestranol, norethissterone and norgestrel have been chosen because of their common use as oral contraceptives. The fifth steroid is the anabolic drug methyltestoosterone.
The optimum derivatization and instrumental conditions have been carefully studied before quantitation.
Calibration data and regression equations were quoted for each steroid by measurement of peak height ratios using an I.S .. The GC mean percent recovery of pure steroids are 99.17 + 1.53 - 103.00 + 3.39
The GC method proved to be sensitive and selective for each investigated steroid. The method has been applied to analysis of combined steroid formulations. Microvlar 30, Nordette, Triovlar (triphasic preparation) Norminest Fe, Norinyl 1 and Ethinyl Estradiol tablets were successfully assayed following this GC method. Simultaneous determination of both oestrogenic and• progestogenic components was achieved with all tablets except Norinyl 1 where preseparation of both components was carried out. Mean percent recoveries were found to be within the range 91.80 + 3.49 to 107.17 + 1.66. Methyltestosterone was assayed in both bulk powder and in tablets as its MO-DMES and DMiPS ether derivatives. The latter derivative has proved higher sensitivity and accuracy. Mean percent recoveries are 100.70 + 0.71 and 100.43 + 0.821 respectively.
By using GC-MS-SIM technique of analysis, the sensitivity of the method has increased by about ten folds. Mean percent recoveries of
pure bulk steroids are 98.32 ~ 1.401 to 99.80 + 2.066. This techniique permits assay of as low as 5 ng/ul steroid. Accordingly, Norinyl 1 tablets were assayed directly without previous separation. Assay results of six oral contraceptive preparations are compairable with those obtained using the GC method. Mean percent recoveries range from 96.42 + 0.645
to 102.26 + 3.749.
PART VI
This part describes a new contripution towards identification and quantitative determination of norethisterone metabolites in plasma. Norethisterone has been chosen because it is a potent progestogen which is widely used in oral contraceptive formulations. The GC and GC-MS properties of norethisterone metabolites reference compounds as their MO-DMES and 6~~ DMES ether derivatives has been studied. Pure reference compounds were also used to establish the optimum extraction conditions of these compounds from spiked plasma. Linearity of recovery from spiked plasma has been confirmed from the correlation coefficient values.
Following the GC-MS-SIM technique of analysis, the mean percent recoveries were found to be within the range 94.96 + 1.54 to 97.38 + 2.14 .
Noretllisterone and its metabolites have been identified and quanntified by GC-MS-SIM in a volunteer plasma samples 0.5-8 h following administration of 2 Norinyl 1 tablets (1 mg norethisterone per tablet).
The use of DMES ether derivatives offers characteristic and highly abundant ions at high mlz values and hence increases the sensitivity and accuracy of the method.
This thesis comprises 27 Tables, 24 Figures, 3 Schemes and 290 References.