الفهرس 
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Abstract
This thesis deals with the analysis of the antifungal drug posaconazole using several analytical methods.
In addition, the simultaneous HPLC determination of posaconazole and the antineoplastic agent, vincristine was proposed. Moreover, this work investigates the effect of different elevated lipoprotein levels on the pharmacokinetics of posaconazole and vincristine when they are solely and co-administered in rat.
This thesis comprises six parts:
<Part I General Introduction and Literature Review This part contains a general introduction about the chemical names, structures, physical properties, pharmacological actions and therapeutic uses of the studied drugs. It also contains literature reviews for the pharmacopoeia and other reported methods of analysis for the selected drugs in pharmaceutical dosage forms, biological samples and other possible matrices.
<Part II
High performance liquid chromatographic assay for the simultaneous determination of posaconazole and vincristine in rat plasma
<This part presents a validated HPLC-DAD method for the simultaneous determination of posaconazole (PSZ) and vincristine (VCR) in rat plasma. PSZ and VCR along with the internal standard (itraconazole, ITZ) were extracted from 200 μL plasma using liquid-liquid extraction with diethyl ether in the presence of 0.1 M sodium hydroxide solution.
After vortexing and centrifugation, the organic layer was transferred to clean tubes and evaporated in vacuo. The dried residue was reconstituted in methanol and injected into the HPLC through HC-C18 (4.6 × 250 mm, 5 μm) column. The mobile phase consisted of acetonitrile and 0.015 M potassium dihydrogen orthophosphate, (30:70 to 80:20, linear gradient over 7 minutes) pumped at 1.5 mL/min. Detection wavelengths were 220 and 262 nm for VCR and PSZ respectively. Sprague Dawley rats (n=2) were orally dosed PSZ 40 mg/kg followed by iv dosing of 0.1 mg/kg VCR 30 minutes later. Serial blood sampling was performed at 0.5, 0.75, 1.0, 1.5, 2.0, 3.5, 6.0, 8.0, 12, 24, 48 and 72 h post oral dose. The three compounds (VCR, PSZ and ITZ) were successfully separated within 11 min. Calibration curves were linear (r2 ≥ 0.997) over the range of 50-5000 ng/mL for both PSZ and VCR. The CV% and % error of the mean was ≤ 18% for both drugs.
The validated lower limit of quantification was 50 ng/mL for both drugs based on 200 μL rat plasma. Rat plasma concentrations of PSZ and VCR were simultaneously measured up to 72 h. The pharmacokinetics parameters calculated for both drugs were found to be comparable to literature.