الفهرس 
Preface
DiabetesOnly 14 pages are availabe for public view
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Abstract
This thesis is concerned with the densitometric , spectrodensitometric and high
performance liquid chromatographic analysis of some oral hypoglycemic drugs
namely; thiazolidinediones as pioglitazone HCl , second generation sulfonyl ureas
as glibenclamide, gliclazide, glimepiride,glipizide, biguanides like metformin HCl,
and meglinitides for instance repaglinide. It comprises two parts in addition to
general introduction about the investigated drugs and a literature review includes
the official and reported methods for their determination in bulk, pharmaceutical
dosage forms and in biological samples.
PART I:
This part includes five chapters deals with new densitometric and
spectrodensitometric thin layer chromatographic methods for determination of
the studied drugs.
Chapter I:
This chapter concerns with a new, simple, sensitive and selective HPTLCdensitometric
method for the determination of pioglitazone HCl .The method is
based on the reaction of the investigated drug with o-phthaldehyde as spray reagent
and the determination of the produced pink colored product densitometrically
using UVP scanner. Separation was achieved on HPTLC silica gel 60 aluminum
sheets using chloroform and methanol (10:1 v/v) as mobile phase. The obtained Rf
value was 0.51 ± 0.01. The TLC chromatogram image was captured by
the scanner, then the image was loaded into the GelWorks software. Once
the standard known concentrations were assigned, the calibration graph was
generated automatically. The generated graph correlates the concentration with
the corresponding signal intensity represented as raw volume or area under peak.
A study for all the reaction variables was carried out to optimize reaction
conditions. Also a validation study for the proposed procedure according to ICH and USP31-NF26 guidelines was performed. A linear calibration curve was
obtained in the range of 200.0 to 3000.0 ng/spot. The detection and quantitation
limits were 65.06 and 197.16 ng/spot; respectively. The proposed method was
successfully applied for the analysis of pioglitazone HCl in pure and tablets.
Results were compared with those obtained from the reported method. There was
no significant difference according to t- and F- values indicating high accuracy and
good precision of the proposed method.
Chapter II:
This chapter includes a new spectrodensitometric method for analysis of
the investigated drugs .The proposed method depends on salting out thin layer
chromatography for separation of all the studied oral hypoglycemic drugs. This
method has been studied, modeled, evaluated and validated.
The chapter includes a study of salting out thin layer chromatography and
computational analysis of some oral hypoglycemic drugs. In this study,
a quantitative structure–retention relationship study of all investigated oral
hypoglycemic drugs was carried out using a salting-out thin layer chromatographic
technique. Aqueous solution of ammonium sulfate and acetonitrile was used as
a mobile phase. It was established that the applied mobile phase has different
effects on retention of the studied oral antidiabetic drugs. The factors that affect
on the salting-out process were determined. In this study a good correlation
between the structures of the investigated drugs with the retention data and
molecular descriptors was established. This was achieved through out
computational analysis and using molecular operating environment software
(MOE), focusing on octanol/water partition coefficient, molar refractivity, total
hydrophobic surface area, hydrophobic volume, Van der Waals energy and
solvation energy. Quantitative structure–retention relationship modeling for
the separation of the investigated drugs was carried out through one-parameter.