Bazı anjiotensin II antagonisti ilaç karışımlarının fotodiyot dizi dedektör ve kütle spektrometresi ile sıvı kromatografisinde aynı anda analizleri ve validasyonları

---

Thesis Type: Doctorate

Institution Of The Thesis: Ankara University, Sağlık Bilimleri Enstitüsü, ANALİTİK KİMYA ANABİLİM DALI, Turkey

Approval Date: 2019

Thesis Language: Turkish

Student: TUĞBA NEMLİOĞLU

Supervisor: SİBEL AYŞIL ÖZKAN

Open Archive Collection: AVESIS Open Access Collection

Abstract:

The aim of this thesis to develop a liquid chromatographic method using two different detectors which are the DAD and MS/MS for simultaneous determination of olmesartan, valsartan, telmisartan, amlodipine and hydrochlorothiazide from the drug active substances used in the treatment of hypertension. For this reason, experimental conditions such as different mobile phase compositions, temperature, flow rate effects are optimized. The first method based on reverse phase liquid chromatography by using Symetry Shield (150x4.6; 3.5 µm) (Waters, ABD) column and methanol: acetonitrile: pH 3.0 solution (phosphoric acid), 40:40:20, v \ v \ v mobile phase composition. The separation was carried out at 25 ° C, a flow rate of 1 mL min-1 and a detection wavelength of 220 nm. The second method involved MS/MS, Poroshell 120 EC C-18 (50 mm x 3,0 mm x 2,7 μm) (Agilent, ABD) column and acetonitrile: buffer solution (10 mM ammonium formate; formic acid), 40:60, v \ v mobile phase composition. The analyses were carried out at 25 ° C, a flow rate of 0,6 and 0,8 mL min-1 as a gradient. As a result of this study, fast, simple, sensitive, accurate, precise, environmentally and fully validated analysis methods have been developed under optimum working conditions. The proposed rapid and sensitive HPLC-DAD and LC-MS/MS method will be readily applicable in quality control laboratories for simultaneous determination of olmesartan, valsartan, telmisartan, amlodipine and hydrochlorothiazide since they have not a time-consuming sample preparation procedure. The developed methods were also applied to the pharmaceutical dosage forms. Thus, the applicability of the methods in complex matrices such as drug samples have also been demonstrated. Furthermore, student-t and F tests showed that both developed methods were equivalent to each other.