الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
This thesis deals with development of analytical methods for the determination of
some selected drugs of different pharmacological categories acting as enzyme inhibitors.
The thesis comprises five parts:
Part I
This part contains a general introduction about the chemical names, structures,
physical properties, pharmacological actions and uses of the investigated drugs. Detailed
literature reviews are presented showing the reported methods for analysis of the selected
drugs in pharmaceutical preparations, biological fluids and other possible matrices.
Part 11
This part presents a comprehensive stability indicating HPLC with diode array
detection method was developed for determination of the recently approved
phosphodiesterase type 4 (PDE-4) inhibitor roflumilast (RFL). Effective chromatographic
separation was achieved using Durashell C18 column (4.6 X 250 mm, 5 urn particle size)
with isocratic elution of the mobile phase composed of 0.0065 M ammonium acetate pH
6.3, methanol and acetonitrile in the ratio of 30:35:35 (by volume). The mobile phase was
pumped at a flow rate of 1.3 mL/min, and quantification of RFL was based on measuring
its peak areas at 251 nm. RFL eluted at retention time 6.2 min. Analytical performance of
the proposed HPLC procedure was thoroughly validated with respect to system suitability,
linearity, range, precision, accuracy, specificity, robustness, detection and quantification
limits. The linearity range was 2.5-200 ug/ml. with correlation coefficient >0.9998. The
drug was subjected to stress conditions of neutral, acidic and alkaline hydrolysis,
oxidation, photolysis and thermal degradation. The proposed method proved to be
stability-indicating by resolution of the drug from its forced degradation products.
Moreover, specificity of the method was verified by resolution of drug from more than 20
pharmaceutical compounds of various medicinal categories. The validated HPLC method
was successfully applied to the analysis of the cited drug in its tablet dosage form. The
proposed method made use of DAD as a tool for peak identity and purity confirmation.
The validated HPLC method was applied to the analysis of rotlumilast in tablets dosage
form where assay results revealed satisfactory accuracy and precision. The results were
statistically compared to previously published UV spectrophotometric method using
Student’s Hest and variance ratio F-test. The results showed no significant difference
between the proposed and the reference methods.