الفهرس 
General introductionOnly 14 pages are availabe for public view
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Abstract
Many vital compounds containing nitrogen atom have been investigated in our
study. These compounds have been analysed by different analytical methods in different
pharmaceutical dosage form and in biological fluids. These compounds are: Metformin
Hydrochloride (MET), Linagliptin (LNG), Pyridostigmine bromide (PYR) and
Telmisartan (TEL).
Five chapters are included in this thesis:
Chapter 1:
This chapter includes general introduction about each drug illustrating their
chemical structure, IUPAC name, physical and chemical properties. Also literature
review including all reported different methods about each drug are shown.
Chapter 2:
General considerations, apparatus, materials and chemicals are included in this chapter.
Chapter 3: Comparative determination of Metformin HCl and Linagliptin in
Jentadueto® tablets by HPTLC/HPLC-DAD
Two new validated methods for the quantification of Metformin HCL and
Linagliptin by HPTLC-densitometry and reverse-phase high-performance liquid
chromatography procedure coupled with photodiode array detector (RP-HPLC-DAD)
were developed and compared. HPTLC separations were performed using a mobile phase,
methanol: ammonia: glacial acetic acid: formic acid (94.8: 4: 0.6: 0.6 v/v) for Metformin
HCL and Linagliptin. For HPLC-DAD analysis, separation of all compounds was
achieved using an isocratic elution system using a mobile phase, methanol: (0.025M)
potassium dihydrogen orthophosphate buffer at pH=6 (65:35 v/v) .Good resolution and
quantization were achieved. Accuracy and precision, as well as detection and quantitation
limits of the two methods were evaluated and compared .Excellent linearity was observed
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for all of the standard calibration curves, and the correlation coefficients were above
0.999. HPTLC limits of quantitation were 0.47 and 0.17 μg/band for Metformin HCL and
Linagliptin respectively, whereas HPLC limits were 3.5 and 0.788 μg/ml for Metformin
HCL and Linagliptin respectively. In comparison with HPLC, HPTLC is less expensive
and faster procedure, requiring 2–3 h to analyze 10–12 samples on a single plate.
Chapter 4: Analysis of Metformin HCl and Telmisartan in human plasma
This chapter is divided into two parts
A. Introduction about HPLC-MS/MS and its applications
It includes introduction about HPLC-MS/MS, history about the development of
HPLC-MS/MS and its principle of action. Also component of the instrument has been
illustrated. It composed mainly of two parts HPLC and Mass spectrometer.
Component of Mass spectrometer has been studied showing types of ion sources, analyzer
and detector.
Many applications of HPLC-MS/MS have been stated including: Natural products,
Pharmacokinetics, Forensic science, Agro chemistry, Food analysis, Petro chemistry,
Cosmetics and Proteomics.
B. Development and validation of a UPLC–MS/MS method for the simultaneous
determination of Telmisartan and Metformin HCl in human plasma
A new sensitive, rapid, precise and robust method has been developed for
determination of Metformin hydrochloride and Telmisartan in human plasma using
Losartan potassium as internal standard by Ultra Performance Liquid chromatography
coupled with mass detector and positive electro spray ionization as method of analyzer.
The mobile phase was composed of Acetonitrile: water: formic acid (89.2: 10.7:0.1 v/v)
with flow rate 250μl/min and injection volume was 10 μl at room temperature.
85 The stationary phase used was Hypersil-Gold column 50 mm x 2.0 mm (1.9 μm) from Thermo Scientific, New York, USA. The optimized SRM transitions (precursor ion m/z→
product ion m/z) were 515.40 → 276.05 for TEL, 130.2 → 55.31 for ME, and 423.03 →
207.05 for LOS. Six volunteer`s plasma samples have been analysed after taking 500 mg Metformin hydrochloride ( Cidophage® ) and 40 mg Telmisartan (Micardis® ) . The human samples have been extracted by liquid-liquid extraction method using acetonitrile as protein precipitating agent.
Pharmacokinetic study has been applied and pharmacokinetic parameters as T max, C max,
t1/2, K el and AUCinf have been illustrated.
Chapter 5: A stability-indicating HPLC method for the determination of
Pyridostigmine bromide in commercial tablets.
A stability indicating assay method for determination of pyridostigmine bromide and its degradation product using High Performance Liquid chromatography coupled with diode array detector (HPLC-DAD) has been illustrated in this chapter. Separation of Pyridostigmine bromide and its degradation products have been occurred using isocratic method with mobile phase acetonitrile: ammonium acetate method at pH=6(5:95) withflow rate 1ml/min at 270 nm and injection volume 90 μl. The stationary phase was C18column (250mm × 4.6 mm i.d.) was made of stainless steel and packed with Inertsil ODS-
3v (5 μm particle diameter, GL Sciences, Tokyo, Japan). Pyridostigmine bromide hasbeen directed to acid, alkaline and oxidative stress conditions. The degradation productshave been identified using positive electron spray spectrometry (UPLC-ESI (+)-MS)detection. Pyridostigmine bromide was found to be unstable in alkaline media while it ismore stable in acidic media. Pyridostigmine bromide should be kept in tightly closedbottle as its easily oxidized