الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
This study describes spectrophotometric and fluorimetric methods for the
analysis of five therapeutically important and widely used calcium channel antagonist
drugs. These drugs are nifedipine (NIF), nicardipine hydrochloride (NIC), nimodipine
(NIM), felodipine (FEL) and amlodipine besylate (AML). The drawbacks encountered
in the analytical methods reported in literatures for the analysis of these drugs were
our interest in selection of these drugs to be the target of this study.
In this thesis sevsral analytical methods have been developed for the determination
of 1, 4-DHP. The developed methods are classified into general and selective
methods.
1. GENERAL METHODS
1.1. Oxidation Methods
Two oxidation spectrophotometric methods and one fluorometric method
were developed and validated for determination of the investigated drugs via
oxidation with potassium permanganate and ceric ( IV) ammonium sulphate in acidic
medium.
1.1.1. Using Potassium Permanganate in acid medium
Our present work is a new study for assay 1, 4-DHP drugs in acidic medium
using KMnO4. It is an oxidation-based spectrophotometric method which was applied
and validated for determination of 1, 4-DHP drugs via their oxidation with potassium
permanganate in sulphuric acid. The concentrations of the drugs in their samples
were determined by measuring the decrease in the absorption intensity of the pink
colour of permanganate at 525 nm. Different variables which affected the reaction
conditions were carefully studied and optimized for each investigated drugs.
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1.1.2. Using Ce (IV) in acid medium (Spectrophotometrically)
Ce (IV) was used before for determination of NIF, NIM and FEL as titrimetric
method using ferroin indicator or spectrophotomerically with NIM through direct
measurement of produced cerium (III), spectrofluorometric with NIF and Kinetic
spectrofluorometric with NIC.
Our present work is a new assay of 1, 4-DHP drugs using p-DMAB as a
second reagent for determination the excess Ce (IV). It is an oxidation-based
spectrophotometric method which was applied and validated for determination of 1,
4-DHP drugs via their oxidation with Ce (IV) in perchloric acid and measuring the
difference in the absorption intensity (ΔA) at 464 nm. Different variables affecting the
reaction conditions were carefully studied and optimized for each investigated drugs.
1.1.3. Using Ce (IV) in acid medium (Spectrofluorometrically)
The aim of the present study was directed to the development of new
simple spectrofluorimetric method for analysis of drugs in pharmaceutical dosage
forms. It is an oxidation-based direct spectrofluorometric method which was applied
and validated for determination of 1, 4-DHP drugs via their oxidation with Ce (IV) in
sulphuric acid and direct monitoring the fluorescence of the produced cerium (III) at
355 nm (excitation at 255 nm) which proportional with the concentrations of the
drugs in their samples. Different variables affecting the reaction conditions were
carefully studied and optimized for each investigated drugs.
1.2. Bromination and Coupling Method Using NBS and INC, PAP
This part describes a spectrophotometric method for determination of all
the 1, 4-DHP through their bromination of the active methylene group with Nbromosuccinimide
(NBS) reagent and subsequent treatment of the residual NBS with
indigo carmine (INC) and p-aminophenol (PAP) as dyestuffs. The formed coloured
products were measured spectrophotomerically at 607 and 556 nm for NBS/INC and
NBS/PAP method respectively. The method was applied before on some 1, 4-DHP
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drugs using bromate-bromide mixture and our present work is a continuation of the
previous study for application on 1, 4-DHP drugs in different conditions using other
more safe reagents rather than BrO3
- / Br- mixture.
Different variables affecting the reaction conditions were carefully studied
and optimized for each particular reagent (chromogenic or conditioning) with all the
investigated drugs.
2. SELECTIVE METHODS
The previous methods are considered as general non-selective methods for
quantification of all the studied 1, 4-DHP drugs. In searching for selectivity some
nucleophilic reagents were tried successfully in this field where they could be applied
only for 1, 4-DHP drugs that contain either active methylene group which attached
with dihyDROPyridine ring or basic center (forming ion pair complex) or nitro group
which can be reduced to aromatic primary amine.
2.1. Vanillin Method
A new simple and specific spectrophotometric method, which is developed
for the determination of the studied drugs by reaction with vanillin in presence of
conc. hydrochloric acid. The method depends on the interaction of the active
methylene group exist in a drug molecule with vanillin which results in the formation
of coloured substituted product. The increase in the absorption intensity was
measured at 500 nm for NIF, NIC, NIM, FEL and 479 nm for AML. A study for all
variables was carried out to optimize the reaction conditions. A validation study for
the proposed procedure according to USP 2002 was also performed.
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2.2. Tetrabutylammonium hydroxide Method
While the 1, 4-DHP drugs are mostly behave as weak acids thus upon
treatment with strong bases they afford the corresponding anions and appreciable
red shift occur. So; the addition of TBAH base to all 1, 4-DHP drugs in
dimethylsulphoxide (DMSO) produces a pronounced bathochromic effect; which is
due to anion formation in the basic medium utilizing the proton in 1, 4-DHP ring.
Different variables affecting the reaction conditions (type of base and the
organic solvent) were carefully studied and optimized with the investigated drugs
2.3. Non-Extractive Ion-Pair Formation Method Using eosin Y
This study describes a generic non-extractive spectrophotometric procedure
for determination of NIC and AML by formation of coloured ion-pair complexes with
eosin Y reagent in buffered medium using methylcellulose as surfactant. The formed
ion-pair complexes were measured spectrophotomerically at 549 nm. Different
variables affecting the reaction conditions were carefully studied and optimized for
each particular parameter with the investigated drugs.
2.4. Schiff’s base Method Using p-DMAB reagent
This method was applied before for determination of NIM. And in this study
a continuation of the previous one for the determination of NIF and NIC; containing
nitro group. which were reduced with Zn0/HCl mixture then react with p-DMAB to
form Schiff’s base. This reaction yielded a coloured reaction product which can be
measured at 434 and 441 nm for NIF and NIC respectively. Different variables
affecting the reaction conditions were carefully studied and optimized for particular
reagent with NIF and NIC.