Hussein Nabil Mahfouz Ghanem, <br/><br/>
Development and validation of new analytical methods for the determination of some drugs used in treatment of CNS disorders / 
 اﻟﺘﻄﻮﯾﺮ واﻟﺘﺤﻘﻖ ﻣﻦ ﻓﺎﻋﻠﯿﺔ ﺑﻌﺾ اﻟﻄﺮق اﻟﺘﺤﻠﯿﻠﯿﺔ اﻟﺠﺪﯾﺪة ﻟﺘﻘﺪﯾﺮ ﺑﻌﺾاﻷدوﯾﺔ اﻟﺘﻲ ﺗﺴﺘﺨﺪم ﻓﻲ ﻋﻼج اﻣﺮاض اﻟﺠﮭﺎز اﻟﻌﺼﺒﻰاﻟﻤﺮﻛﺰى 
by Hussein Nabil Mahfouz Ghanem ; Supervised Prof. Dr. Asmaa Ahmed El Zaher, Prof. Sally Tarek Mahmoud, Dr. Enas Taha Abdelhamed. 
 - 137 pages :  illustrations ;  25 cm. +   CD. 
<br/><br/>Thesis (M.Sc)-Cairo University, 2025. 
<br/><br/>Bibliography: pages135–137.  
<br/><br/> Based on the principles of green and white analytical chemistry, new <br/>univariate and chemometric-aided UV spectrophotometric techniques were <br/>created for the simultaneous determination of olanzapine (OLA), fluoxetine HCl <br/>(FLU), and its toxic impurity 4-(Trifluoromethyl) phenol (FMP), without the <br/>need for earlier separation. Through dual-wavelength ratio spectrum analysis, <br/>OLA (4-20 ȝg/mL) and FLU (5-50 ȝg/mL) were successfully determined in the <br/>presence of FMP with satisfactory performance characteristics, including 98-<br/>102% accuracy and precision (RSD <2%). the method was complied with ICH <br/>standards. Chemometric techniques, including partial least squares (PLS) and <br/>artificial neural networks (ANNs), demonstrated superior performance with Latin <br/>hypercube sampling (LHS) for systematically generate representative validation <br/>sets, overcoming the limitations of conventional random data. The analytical <br/>methods were validated across concentration ranges of 2-20 ȝg/mL for both OLA <br/>and FMP, and 5-50 ȝg/mL for FLU. The PLS model demonstrated root mean <br/>square errors of prediction (RMSEP) of 0.087, 0.048, and 0.159 for OLA, FMP, <br/>and FLU respectively. Superior performance was observed with ANN, showing <br/>lower RMSEP values (0.056, 0.047, and 0.087), respectively. Environmental <br/>impact was evaluated using multiple assessment tools including NEMI, ESA, <br/>Complex GAPI, AGREE, and RGB 12 metrics., demonstrating strong <br/>environmental compliance. Statistical analysis revealed no significant <br/>differences (P > 0.05) compared to existing methods. The methods were <br/>successfully applied to pure powders and pharmaceutical capsules. <br/>A novel, eco-friendly high performance liquid chromatography (HPLC) <br/>method was developed for the simultaneous determination of pregabalin (PRE), <br/>milnacipran hydrochloride (MIL), and duloxetine hydrochloride (DLU), FDA-<br/>approved fibromyalgia drugs. This method addresses challenges posed by their <br/>structural diversity and PRE's poor UV absorbance. With the aim of reducing run <br/>time and eliminating derivatization, it avoids hazardous reagents and reduces <br/>waste. Separation was achieved on a C18 column using a mobile phase of 45% <br/>0.03M sodium dihydrogen phosphate buffer (pH 3.5), 30% acetonitrile, and 25% <br/>methanol at flow rate 0.9 ml/min, with UV detection at 210 nm. The method <br/>showed extended linearity (100–1600 μg/ml for PRE, 2–40 μg/ml for MIL and <br/>DLU) and quantification limits of 91.2, 1.326, and 1.872 μg/ml, respectively. <br/>Validated per ICH guidelines and applied to pure drugs and formulations, its <br/>sustainability was confirmed by AGREE and Complex GAPI greenness <br/>assessments. <br/>An innovative chemometrics-assisted UV spectrophotometric methods <br/>for simultaneous quantification of cinnarizine (CIN), domperidone (DOM), and <br/>benzophenone (BNZ), a carcinogenic CIN degradation product, achieved without <br/>the need for prior separation. Predictive models using Classical Least Squares <br/>(CLS), PLS, and Multivariate Curve Resolution–Alternating Least Squares <br/>(MCR-ALS) were developed, with a strategically optimized validation set of 13 <br/>mixtures generated via MATLAB’s Candexch algorithm (D-optimal design). <br/>The methods exhibited robust linearity across 4–20 μg/mL (CIN), 3–15 μg/mL <br/>(DOM), and 1–5 μg/mL (BNZ). Calibration performance was excellent, with root <br/>mean square errors of calibration (RMSEC) values of 0.036–0.062 (CLS), 0.013–<br/>0.024 (PLS), and 0.009–0.012 (MCR-ALS), with MCR-ALS demonstrating the <br/>highest accuracy and stability. Validation confirmed recovery rates of 98–102%, <br/>while RMSEP values for the validation set ranged from 0.042–0.201 (CLS), <br/>0.035–0.187 (PLS), and 0.022–0.154 (MCR-ALS), with MCR-ALS consistently <br/>outperforming other methods in predictive accuracy. Environmental <br/>sustainability was extensively assessed using NEMI, Complex GAPI, AGREE, <br/>BAGI, RGB12, Spider Chart, Carbon Footprint Analysis, GSST, and the NQS <br/>Index, confirming exceptional eco-friendliness and alignment with (UN-SDGs). <br/>A novel environmentally friendly analytical method utilizing Fourier <br/>Transform Infrared (FTIR) spectroscopy was developed for the simultaneous <br/>quantification of CIN and DOM without the need for prior separation. The <br/>approach is based on analyzing the first derivative spectra within the infrared <br/>range of 4600–FPၱï&,1LVTXDQWLILHGDWFPၱïZKHUH'20]HUR<br/>FURVVLQJDQG'20LVGHWHUPLQHGDWFPၱïZKHUH&,1VKRZV]HURFURVVLQJ<br/>The method exhibited excellent linearity within the concentration ranges of 0.6-<br/>3.3 μg/mg for CIN and 0.4–2.4 μg/mg for DOM. Additionally, the limits of <br/>detection (LOD) for both drugs were determined to be 0.171 and 0.128 μg/mg <br/>for CIN and DOM respectively, confirming the method’s sensitivity. The <br/>developed method was validated according to ICH guidelines and successfully <br/>applied to both pure substances and pharmaceutical formulations.   تقدم هذه الرسالة استراتيجية تحليلية شاملة لتحديد كميات الخلطات الصيدلانية المعقدة المستخدمة في علاج اضطرابات الجهاز العصبي المركزي (CNS).تدمج هذه الاستراتيجية تقنيات التحليل الطيفي المتقدمة، وبشكل خاص التحليل الطيفي بالأشعة فوق البنفسجية (UV) والتحليل الطيفي بالأشعة تحت الحمراء باستخدام تحويل فورييه (FTIR) ، مع طرق الكروماتوغرافيا مثل الكروماتوغرافيا السائلة عالية الأداء (HPLC) .تستخدم الدراسة طرق احادية مثل طيف النسبة ذو الطول الموجي المزدوج ، وتحليل الطيف المشتق، بالإضافة إلى عدد من أدوات الكيمياء الحسابية (الكيمومتريكس) ، بما في ذلك المربعات الصغرى الكلاسيكية (CLS) ، والمربعات الصغرى الجزئية (PLS) ، والشبكات العصبية الاصطناعية (ANNs) ، وحل المنحنيات المتعددة المتغيرات - المربعات الصغرى المتناوبة (MCR-ALS)، لتعزيز تفسير البيانات وأداء الطريقة.تم إجراء تصميم التجارب والتحقق من النموذج باستخدام أخذ العينات من الهيبركيوب اللاتيني (LHS) وتصميم   D- optimal المنفذ عبر خوارزميةcandexchفي  MATLAB. وقد ضمنت هذه الطريقة متانة الطريقة، والدقة، والكفاءة التشغيلية مع الحفاظ على الاستدامة البيئية.أظهرت المنهجيات المطورة دقة عالية، وموثوقية، وكفاءة بيئية، مما يجعلها مناسبة لمراقبة الجودة الصيدلانية الحديثة. تم إجراء تقييمات للون الأخضر، واللون الأبيض، واللون الأزرق، إلى جانب اختيار المذيبات الموجه بواسطة أداة اختيار المذيبات الخضراء (GSST) ومخطط العنكبوت لتقييم مؤشر الخضرة. (SDAGI) أكدت التقييمات باستخدام مؤشر الطرق البيئية الوطنية (NEMI)، ومقياس البيئة التحليلية (ESA)، ومؤشر الإجراءات التحليلية الخضراء التكميليالمعقد (Complex GAPI)، ومقياس الخضرة التحليلية (AGREE)، وتحليل البصمة الكربونية، ومؤشر قابلية الاستخدام الأزرق (BAGI) ، ونموذج الأحمر والأخضر والأزرق 12 (RGB12)، ومؤشر الحاجةو الجودة والاستدامة (NQS)على الالتزام القوي بمبادئ الكيمياء التحليلية الخضراء (GAC) والكيمياء التحليلية البيضاء (WAC). ومواءمته مع أهداف التنمية المستدامة للأمم المتحدة.(UN-SDGs) 
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<br/><br/><br/>Text in English and abstract in Arabic & English. 
<br/><br/><label>Subjects--Topical Terms: </label><br/>Pharmaceutical Chemistry<br/>الكيمياء الصيدلية
<br/><br/><label>Subjects--Index Terms: </label>UV spectrophotometry  Fourier transform infrared (FTIR)  high- performance liquid chromatography (HPLC)  chemometrics and univariate  techniques  experimental design  environmental sustainability  تحليل الأشعة تحت الحمراء بتحويل فورييه (FTIR)  التحليل الطيفي بالأشعة فوق البنفسجية (UV) 
<br/><br/><label>Dewey Class. No.: </label>615.19