الفهرس 
General IntroductionOnly 14 pages are availabe for public view
 |  | from | 156 |  |  |
| | | from | 156 | | |
Abstract
The compounds investigated throughout this work were determined in
laboratory prepared mixtures, different pharmaceutical dosage forms, the presence of
degradation products, and biological fluids. These compounds include sofosbuvir
(SOF), ledipasvir (LED), pseudoephedrine hydrochloride (PSE), paracetamol (PAR),
caffeine (CAF), cetirizine dihydrochloride (CET), guaifenesin (GUA), ibuprofen
(IBU), and atenolol (ATE).
The thesis consists of four chapters:
Chapter 1
Includes a general introduction about the pharmacological effects of the studied
compounds, their structures, physical properties such as melting point, molecular
formula, molecular weight, and solubility in different solvents.
Chapter 2
This chapter is divided into four parts:
A-General introduction to green chemistry, which includes some important
definitions of green chemistry, a simple background about the history and beginning of
green chemistry, and a discussion of the twelve principles of green chemistry.
B- General introduction to green analytical chemistry, including definitions,
importance, objectives, and discussion of the twelve principles of green analytical
chemistry. In addition to the challenges facing it and the strategies for greening the
analytical methods.
C- General introduction to hazardous and green solvents and different solvent
selection guides. In addition to the assessment of the greenness of the methods through
different metrics, the national environmental methods index (NEMI), the green
analytical procedure index (GAPI), the analytical greenness metric (AGREE), and the
analytical eco scale assessment.
D- General introduction about the application of green analytical chemistry in
the pharmaceutical analysis field, which includes strategies and examples for greening
different methods for analysis of pharmaceutical products, e.g., titrimetric methods,
spectrophotometry, spectrofluorometry, near-infrared (NIR) spectroscopy, flowinjection
analysis (FIA), raman spectroscopy, electroanalysis, liquid chromatography,
126
gas chromatography, supercritical fluid chromatography (SFC), and high performance
thin layer chromatography (HPTLC).
Chapter 3
A simple, rapid, inexpensive, and eco-friendly HPTLC method with
densitometric detection was designed, optimized, and validated for the simultaneous
quantitation of the antiviral drugs sofosbuvir (SOF) and ledipasvir (LED) in pure
powder, synthetic mixtures, combined pharmaceutical formulation, and in the presence
of their stressed degradation products with high sensitivity and no interference. The
separation was carried out on silica gel F254 plates using green mobile phase ethyl
acetate: water: ethanol (94:5:1v/v/v) for development, followed by densitometric
detection of SOF and LED at 250 and 320 nm, respectively. Both drugs had second
order polynomial calibration curves within ranges of 100–5000 ng/spot and 100–3000
ng/spot for SOF and LED, respectively, with correlation coefficients >0.9998, and the
limits of detection were 30 and 29 ng/spot, and the limits of quantification were 90 and
88 ng/spot for SOF and LED, respectively. The method was validated in terms of
linearity, accuracy, precision, selectivity, and robustness. The drugs were subjected to
acidic and alkaline hydrolysis, oxidation, and photolytic conditions as per ICH
guidelines, followed by detection and characterization of the degradation products and
structure elucidation of their fragments with the aid of the HPTLC-ESI- MS technique.
The greenness of the proposed method was assessed using NEMI, and GAPI metrices
in addition to the analytical Eco-Scale assessment with a 93-point score. So, it is
considered excellent green.
Chapter 4
An environment friendly RP-HPLC method was presented for simultaneous
determination of six common cold drugs; PSE, PAR, CAF, GUA, CET, and IBU,
employing some principles of GAC. The HPLC separation and quantitation were made
on a 125 x 4 mm (i.d.) Nucleodur (5 μm particle size) reversed phase C18 analytical
column. The mobile phase was ethanol as mobile phase A, and mobile phase B was
0.1% acetic acid in water. The gradient program consisted of 0-4.5 min isocratic at 20%
mobile phase A; 4.5-5 min gradient up to 95% mobile phase A; 5-9 min isocratic flow
held at 95% mobile phase A; then the flow was returned to the initial composition, and
the analytical column was reconditioned for 10 min before each analysis. The flow rate
was 1.2 ml/min. All determinations were performed at 30°C. The injection volume was
127
20 μl. The detector was set at 215 nm. The mobile phase was filtered before injection
using a 0.45 μm membrane filter. Data acquisition was performed using Clarity
software. The method was validated according to the ICH guidelines and found to be
linear, specific, sensitive, accurate, precise, and robust. The method has been applied
successfully to twelve different pharmaceutical dosage forms including drops, capsules,
and tablets, with high accuracy and selectivity without interference from the commonly
used excipients. Thus, it is a good eco-friendly alternative for the routine analysis of
the investigated drugs in quality control laboratories. The method complies with the
principles of GAC as it takes a short time (9 min) for the analysis of multianalytes in a
single run without derivatization or sample pretreatment, along with moderate energy
consumption. It proved to be highly green according to the recent GAPI and AGREE
metrics, with an eco-scale score of 92 points.
Chapter 5
An environment-friendly, sensitive, simple, and economic spectrofluorimetric
method for the analysis of ATE in pure powder, pharmaceutical preparations, and urine
using green solvents was developed. The analysis was carried out using the solvent 0.02
N NaOH to reach the concentration range of 30-800 ng/ml, and fluorescence intensities
were measured at 301±1nm after excitation at 255 nm using a slit width of 5 nm. The
effects of different solvents, different pHs, and different concentrations of NaOH were
studied. The method was applied successfully to pharmaceutical tablets, spiked urine
samples and real human urine samples. The proposed method was applied to investigate
the urinary excretion pattern of ATE in a healthy male volunteer after oral
administration of 50 mg of ATE in a single dose. Urine samples were collected at
intervals for up to 24 hours. The method was validated according to the ICH guidelines,
proving that it is accurate, specific, precise, and robust. So, it is suitable for quality
control analysis of ATE and for the detection of drug abuse in precision sports because
it is sensitive enough to analyze ATE on a regular basis at therapeutic urine levels. The
method complies with the principles of GAC as it takes a very short time for the analysis
of ATE with high sensitivity, low cost and simple instruments, small energy
consumption, very little waste, and is free from harmful solvents, ensuring operator
safety. The proposed method’s high level of greenness was proved by its high eco-scale
score (95 points) as well as by the GAPI and AGREE greenness assessments.