الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Part I :
This part contains a short account about inflammation and muscle spasm.
The pharmacological action of some anti-inflammatory drugs and muscle relaxants is also discussed.
This part mainly 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 as well as in biological fluids.
<Part II :
The human genome is susceptible to changes either due to intrinsic factors because of errors during replication or extrinsic factors due to interactions with various insults such as pharmaceuticals, pollutants, radiation or chemicals, etc.
<All such changes have the potential to cause apoptosis, carcinogenesis, and mutagenesis.
In this chapter, the potential DNA damaging effect of some anti-inflammatory drugs and muscle relaxants was studied in presence of UVA irradiation.
<Six anti-inflammatory drugs (diclofenac sodium, ketoprofen, leflunomide, naproxen, piroxicam and tolmetin sodium) and a muscle relaxant (tizanidine hydrochloride) were selected.
<Several techniques were developed for DNA damage detection, but many of these methods have complex, time-consuming and expensive procedures.
In this work, simple and sensitive methods (absorption spectroscopy, MALDI-TOF mass spectrometry and fluorescence detection using Tb3+solution) were presented for the detection of strand breaks in double-stranded DNA (dsDNA).
Besides, the effect the studied drugs were examined in presence of UVA on calf thymus DNA real samples.
< All three methods confirmed that all the studied drugs induce nucleic acid damage in presence of UVA except for naproxen.
< Therefore, such anti-inflammatory drugs and muscle relaxants may implicit carcinogenic effects and require some precautions upon their topical or systemic use.>
Part III:
This part comprises three chapters dealing with three stability-indicating HPLC with diode array detection (DAD) methods.
<Chapter I:
<This chapter presents a stability-indicating HPLC with diode array detection (DAD) method for the simultaneous estimation of paracetamol and chlorzoxazone in presence of five of their related substances and potential impurities, namely, 4-aminophenol (AP), p-nitrophenol (NP), acetanilide (AT) and 4-chloroacetanilide (CA) and 2-amino-4-chlorophenol (ACP).
Effective chromatographic separation was achieved using Waters Symmetry C8 (3.9 × 150 mm, 5 μm) with gradient elution of the mobile phase composed 152 of 0.05 M phosphate buffer pH 7.5 and methanol.
<The gradient elution started with 5% (by volume) methanol ramped up linearly to 50% in 10 min, and then maintained at this percentage afterwards till the end of the run. The mobile phase was pumped at a flow rate of 1.0 mL/min.
The multiple wavelength detector was set at 244 and 285 nm to quantify PAR and CZ, respectively.
Additionally, the wavelength 270 nm was found suitable for monitoring PAR, CZ and their related substances.
< The retention times for paracetamol and chlorzoxazone were about 5.7 and 13.5 min respectively.
The reliability and analytical performance of the proposed HPLC procedure were statistically validated with respect to linearity, range, precision, accuracy, specificity, robustness, detection and quantitation limits.
< Calibration curves were linear in the ranges of 10-75 and 10-100 g/mL for paracetamol and chlorzoxazone, respectively with correlation coefficients not less than 0.9998.
<The proposed method proved to be specific and stability-indicating by resolution of the two drugs from their related substances and potential impurities. The validated HPLC method was successfully applied to the analysis of PAR and CZ in their combined formulation (capsules dosage form), and the assay results were favorably compared with a previously reported reference HPLC method. The proposed method made use of DAD as a tool for peak identity and purity confirmation.
<Chapter II:
<This chapter illustrates a stability-indicating HPLC with diode array detection (DAD) method for the simultaneous estimation of paracetamol and lornoxicam in presence of five of their related substances and potential impurities, namely, 4-aminophenol (AP), p-nitrophenol (NP), acetanilide (AT) and 4-chloroacetanilide (CA) and 2-aminopyridine (APD).
Effective chromatographic separation was obtained using XTerra C18 (5 μm, 4.6 x 250 mm) with gradient elution of the mobile phase composed of 0.025 M phosphate buffer pH 6 and acetonitrile.
<The gradient elution started with 5% (by volume) acetonitrile ramped up linearly to 40 % in 10 min, and then maintained at this percentage afterwards till the end of the run.
<The mobile phase was pumped at a flow rate of 1.0 mL/min.
<The multiple wavelength detector was set at 260 nm to quantify PAR and LOR. Additionally, the wavelength 270 nm was found suitable for monitoring PAR, LOR and their related substances.
<The retention times for paracetamol and lornoxicam were about 7.4 and 13.5 min respectively.
<The reliability and analytical performance of the suggested HPLC method were statistically validated with respect to linearity, range, precision, accuracy, specificity, robustness, detection and quantitation limits.
<Calibration curves were linear in the ranges of 10-100 and 10-60 g/mL for paracetamol and lornoxicam, respectively with correlation coefficients not less than 0.9997.
<The suggested method confirmed to be specific and stability-indicating by resolution of the two drugs from their related substances and potential impurities.
<The validated HPLC method was successfully utilized to the analysis of PAR and LOR in their combined formulation (laboratory-made tablets), and the assay results were favorably compared with an already reported reference HPLC method.
The suggested method used of DAD to confirm peak identity and purity.
< Chapter III:
< This chapter represents a stability-indicating HPLC with diode array detection (DAD) method for the simultaneous estimation of paracetamol, aceclofenac, and tizanidine in presence of six of their related substances and potential impurities, namely, 4-153 aminophenol (AP), p-nitrophenol (NP), acetanilide (AT) and 4-chloroacetanilide (CA), 2,6-dichloroaniline (DCA) and diclofenac sodium (DIC).
Successful chromatographic separation was achieved using Waters Symmetry C18 (3.9 × 150 mm, 5 μm) with gradient elution of the mobile phase consisted of 0.025 M phosphate buffer pH 5 and acetonitrile.
<The gradient elution started with 5% (by volume) acetonitrile increased linearly to 50% in 10 min, then remained constant at this percentage till the run was completed.
The mobile phase was pumped at a flow rate of 1.0 mL/min. The multiple wavelength detector was adjusted at 244, 276 and 320 nm to quantify PAR, AC and TZ, respectively.
Additionally, the wavelength 230 nm was selected for monitoring of the combined mixture of PAR, TZ, AC and their related substances.
The retention times for paracetamol, tizanidine and aceclofenac were about 3.99, 4.46 and 10.39 min respectively.
< The reliability and analytical performance of the suggested HPLC method were statistically validated with respect to linearity, range, precision, accuracy, specificity, robustness, detection and quantitation limits. Calibration curves were linear in the ranges of 10-100 g/mL for paracetamol, tizanidine and aceclofenac with correlation coefficients not less than 0.9998.
< The proposed method assured to be specific and stability-indicating by resolution of the three drugs from their related substances and potential impurities.
< The validated HPLC method was effectively employed to the analysis of PAR, AC and TZ in their combined formulation (laboratory-made tablets), and the assay results were favorably compared with an already reported reference HPLC method.
<Part IV:
This part deals with the development and validation of several spectrophotometric methods for the determination of baclofen (BAC) in pure form and in its tablets dosage form.
The methods are based on the reaction of baclofen with vanillin in borate buffer pH 11.5 (method I), Eosin Y in citric-phosphate buffer pH 2.2 (method II) and Hantzsch condensation reaction with formaldehyde and acetylacetone (method III).
The studied reactions utilize the basic primary amine group in the drug to form different colored products upon reactions with the different derivatization reagents.
< Spectrophotometric measurements were achieved by recording the absorbances at λmax 401, 548 and 339nm for the reaction with method I, method II and method III, respectively.
<The different experimental parameters affecting the development and stability of the produced colors were carefully studied and optimized.
< The three methods were validated with respect to linearity, ranges, precision, accuracy and limits of detection and quantitation.
Beer’s law was obeyed in the concentration ranges of 10–35, 5–20 and 5–25 μg/mL for methods I, II and III, respectively with correlation coefficient values not less than 0.999. Additionally, detection limits of BAC are 1.59, 0.94 and 0.79 μg/mL for methods I, II and III, respectively.
<The proposed methods were successfully applied for the assay of the drug in its tablets dosage form.
< Recovery data obtained by the proposed methods were favorably compared with those obtained by a reported HPLC method using the one-way analysis of variance test (single factor ANOVA).
<In addition, illustrative proposed reaction pathways showing the reaction of BAC with the three derivatization reagents were presented.
The thesis consists of 192 pages and comprises 25 tables, 56 figures, and 493 references and ends with an Arabic summary.