فهرست:
خلاصه فارسی ...................................................................................................................................... 1
مقدمه ................................................................................................................................................... 3
فصل اول: کلیات
1-1. بیان مساله. 6
1-2. اهداف.. 6
فصل دوم: بررسی متون و مطالعات دیگران در این زمینه
2-1. مروری بر روش‌های استخراج مایع- مایع و میکرواستخراج مایع- مایع. 8
2-1-1. میکرواستخراج فاز مایع. 9
2-1-1-1. میکرواستخراج فاز مایع با تک قطره 9
2-1-1-2. میکرواستخراج فاز مایع با فیبر توخالی (HF-LPME) 11
2-1-1-2-1. اصول استخراج و سیستم‌های مختلف در استفاده از HF-LPME .. 12
2-1-1-2-2. جنبه‌های عملی و پیکربندی‌های مختلف HF-LPME. 15
2-1-1-2-3. میکرواستخراج فاز مایع از فضای فوقانی با فیبر توخالی. 18
2-1-1-3. میکرواستخراج فاز مایع با استفاده از انجماد حلال استخراج کننده 21
2-1-1-4. میکرواستخراج فاز مایع- مایع پخشی (DLPME) 21
2-1-2. استخراج فاز جامد. 22
2-2. کروماتوگرافی. 22
2-2-1. دسته‌بندی روش‌های کروماتوگرافی. 23
2-2-1-1. کروماتوگرافی مایع با کارایی بالا (HPLC) 23
2-2-1-2. دستگاه‌های کروماتوگرافی مایع. 25
2-2-1-2-1. مخزن فاز متحرک.. 26
2-2-1-2-2. سیستم‌های پمپ کننده 26
2-2-1-2-3. سیستم‌های تزریق نمونه. 27
2-2-1-2-4. ستون‌های کروماتوگرافی مایع. 28
2-2-1-2-5. دمای پیستون. 29
2-2-1-2-6. آشکارسازها 29
2-3. بررسی مطالعات HF-LPME. 33
2-4. بررسی داروی مورد مطالعه. 35
2-4-1. فارماکوکینتیک دارو 35
2-4-2. مکانیسم اثر دارو 35
2-4-3. موارد مصرف دارو 36
2-4-4. منع مصرف و احتیاط. 36
2-4-5. عوارض جانبی. 36
2-4-6. تداخلات.. 36
2-4-7- دوز مصرفی. 36
2-5. اهمیت اندازه‌گیری رالوکسیفن. 37
فصل سوم: مواد و روش ها
3-1. مواد شیمیایی و تجهیزات دستگاهی. 39
3-1-1. مواد شیمیایی، استانداردها و نمونه‌های حقیقی. 39
3-1-2. تجهیزات دستگاهی. 39
3-2. روش استخراج. 40
3-2-1. استخراج به اختصار طی مراحل زیر انجام گرفت: 41
3-2-2. مراحل بهینه‌سازی. 42
3-2-2-1. بهینه‌سازی شرایط جداسازی. 42
3-2-2-2. بهینه‌سازی شرایط استخراج. 42
3-2-2-2-1. نوع حلال آلی. 43
3-2-2-2-2. اثر pH فاز دهنده 43
3-2-2-2-3. اثر pH فاز گیرنده 43
3-2-2-2-4. اثر قدرت یونی فاز دهنده 43
3-2-2-2-5. اثر همزدن محلول آنالیت.. 43
3-2-2-2-6. اثر زمان استخراج. 43
3-2-2-2-7. اثر دما بر استخراج. 43
3-2-3. ارزیابی کارایی روش استخراج. 44
3-2-3-1. منحنی درجه‌بندی. 44
3-2-3-2. تعیین فاکتور پیش تغلیظ (PF) 44
3-2-3-3. تعیین تکرارپذیری (RSD) 45
3-2-4. آنالیز نمونه حقیقی. 45
فصل چهارم: نتایج
4-1. میکرواستخراج سه فازی بر پایه استفاده از فیبر توخالی متخلخل. 47
4-1-1. اصول تئوری. 47
4-2. مراحل بهینه‌سازی. 50
4-2-1. بهینه‌سازی شرایط جداسازی. 50
4-2-2. بهینه‌سازی شرایط استخراج. 51
4-2-2-1. نوع حلال آلی. 51
4-2-2-2. اثر pH فاز گیرنده و فاز دهنده 53
4-2-2-3. اثر سرعت همزدن محلول آنالیت.. 55
4-2-2-4. اثر قدرت یونی فاز دهنده 57
4-2-2-5. اثر زمان استخراج. 58
4-2-2-6. اثر دمای استخراج. 59
4-3. تعیین پارامترهای تجزیه‌ای روش استخراج. 60
4-3-1. تهیه منحنی درجه‌بندی. 61
4-3-2. فاکتور پیش تغلیظ (PF) و درصد بازیابی (R%) 61
4-3-3. تعیین حد تشخیص (LOD) 63
4-3-4. تکرارپذیری روش (RSD) 63
4-4- آنالیز نمونه حقیقی. 64
فصل پنجم: بحث و نتیجه‌گیری
5-1. مقایسه روش استخراجی با روش‌های گزارش شده‌ی دیگر مراجع. 66
5-2. نتیجه‌گیری. 69
منابع................................................................................................................................................... 70
خلاصه انگلیسی................................................................................................................................. 83
ضمائم.................
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Abstract
Raloxifene (sold under the trade name Evista) is an oral selective estrogen receptor modulator (SERM) that has estrogenic actions on bone and anti-estrogenic actions on the uterus and breast. It is used in the prevention of osteoporosis in postmenopausal women.
A three-phase hollow fiber liquid-phase micro extraction (HF-LPME) coupled with high performance liquid chromatography (HPLC) with UV detection method was successfully developed for the determination of trace levels of Raloxifene in human plasma. The analyte was extracted into n-Octanol that was immobilized in the wall pores of a porous hollow fiber from 15ml of aqueous sample, pH:11(donor phase), and was back extracted into the acceptor phase with pH:2.5 located in the lumen of the hollow fiber. The extraction occurred due to a pH gradient between the side of the hollow fiber parameters affecting the extraction process such as type of extraction solvent, donor and acceptor phase pH, extraction time, stirring speed, and salt addition were studied and optimized. Under the optimized conditions (extraction solvent: n-Octanol, donor phase pH:11, acceptor phase pH:2.5, stirring speed: 600 rpm, extraction time: 30 min, enrichment factor of 81% was obtained. Linear dynamic range (LDR) of (1-100) ngmL-1 with good correlation of determination (R2:0.99) and limit of detection (LOD) of 0.3 ngmL-1were obtained for the target drug. The percent relative intraday and inter day standard deviations (RSD%) based on 3 replicate determinations were 2.88% and 3.35% the developed method are simple, rapid, sensitive and are suitable for the determination of trace amounts of Raloxifene in human plasma.
Keywords: Microexrtaction, Hallow Fiber, Pre-concentration, Raloxifene