الفهرس | Only 14 pages are availabe for public view |
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. |