الفهرس 
General introduction
Classification of Antihypertensive DrugsOnly 14 pages are availabe for public view
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Abstract
a) Thesis (M.S.) - Assiut University. Faculty of Pharmacy. Department of Analytical Chemistry.
a) The present thesis concerned with spectrometric and HPTLC analysis of some ARBs
compounds namely: losartan, \irbesartan, valsartan and olmesartan in pure, tablets and
spiked human plasma.
The thesis comprises an introduction and 3 main chapters
Introduction
It is an introductory part which includes general introduction about ARBs, their
medicinal importance, the chemical structure, and physical properties of the target drugs.
The introduction also included a literature review of the official and reported analytical
methods used for the drugs determination. It also included the scope of the research.
Chapter I:
Chapter I includes five simple spectrophotometric methods for determination of
irbesartan and olmesartan and one method for losartan. They were developed for the
determination of the studied drugs through charge transfer reaction between the prepared
salts of the studied drugs as electron donors and p-CA, bromanil, DDQ, picric acid and
TCNQ as electron acceptors. Preparation of the drug salts was used for the first time to
increase electron density on the tetrazole ring which is the site of the reaction and as a
result increase the sensitivity of the proposed methods. The reaction accompanied by
shift of the maxima of the drug from 205 nm to 517, 507, 460, 380 and 842 nm for p-CA,
bromanil, DDQ, picric acid and TCNQ respectively away from the co-formulated HCZ
spectrum which completely overlapped with the spectra of the studied drugs. A study for
all variables was carried out to optimize the reaction conditions.
A validation study was performed for the proposed procedure according to USP XXXI
(2008) and ICH validation guideline (2005). Under the optimal reaction conditions, linear
relationships with good correlation coefficients (0.9984 – 0.9999) were found between
absorbance and concentration of the investigated drugs in the range of 1 – 250 μg/ ml.
The detection limits ranged from 0.15 to 9.90 μg/ ml, while the quantification limits
ranged from 0.46 to 30 μg/ ml. The methods were successfully applied for the analysis of
the studied drugs in pure form and tablets. Results were compared with those obtained by
reported methods. The t- and F values were calculated and compared with the theoretical
values, which indicated high accuracy and precision of the proposed methods.
Summary
157
Chapter II:
Chapter II included a simple and sensitive spectrofluorimetric method for the
quantification of olmesartan, valsartan and irbesartan in bulk, tablets and spiked human
plasma. The method based on measuring the native fluorescence using very simple
procedure. Under the optimal reaction conditions, linear relationships with good
correlation coefficients (0.9989 –0.9998) were found between absorbance and
concentration of the investigated drugs in the range of 1 – 25 ng/ ml. The detection limits
were in the range of 0.10 – 0.40 ng/ ml, while the quantification limits were in the range
of 0.32 – 1.22 ng/ ml. the method was applied successfully for drugs determination in
tablets. The high sensitivity obtained by the proposed methods allowed the determination
of the studied drugs in spiked human plasma, without interference from the constituents
of the plasma.
Chapter III:
This chapter consists of two parts, the first part deals with simultaneous determination of
the studied drugs by two HPTLC methods using reflectance/ absorbance and reflectance/
fluorescence modes. The separation was based on using HPTLC plates pre-coated with
silica gel 60 on aluminum sheets as stationary phase. The mobile phase used composed of
(chloroform: glacial acetic acid 7.5: 2.5 v/v) which allowed complete resolution between
the studied ARBs and this gave the method a great selectivity due to its ability to
distinguish each member. The possibility of simultaneous quantification and
identification of the active ingredient in the finished product is therefore very attractive
from the analytical viewpoint. Under the optimal conditions, linear relationships with
good correlation coefficients (0.9988 – 0.9999) were found between peak area and
concentration of the investigated drugs in the ranges of 90 – 750 ng per band and 2- 120
ng per band for reflectance/absorbance and reflectance/fluorescence methods
respectively. The detection limits were in the range of 14.85 – 30.42 ng per band and
0.55 – 0.81 ng per band, while the quantification limits were in the range of 45.00 –
92.18 ng per band and 1.67 – 2.44 ng per band for the reflectance/absorbance and
Summary
158
reflectance/fluorescence methods respectively. The two methods were applied
successfully for the determination of the studied drugs in tablets and plasma with a good
accuracy and precision.
The second part, involved a stability indicating assay of irbesartan by reflectance/
absorbance and reflectance/ fluorescence modes in pure, tablets and spiked human
plasma by the reflectance/ fluorescence mode without any interference from acidic,
alkaline, oxidative and UV degradations. The degradation pathways under all the studied
conditions were suggested and confirmed by IR and GC Mass spectrometric techniques.
Under the optimal conditions, linear relationships with good correlation coefficients
0.9998 and 0.9974 were found between peak area and concentration of the investigated
drugs in the range of 210 – 900 ng per band and 7- 90 ng per band. The detection limits
were 14.23 ng per band and 1.98 ng per band, while the quantification limits were 43.12
ng per band and 6.02 ng per band for the reflectance.