Artemether’ in Stres Bozundurma Profilinin Stabilite Göstergeli Valide Edilmiş RP-HPLC-DAD Metoduyla Belirlenmesi

Artemether için yeni bir stabilite göstergeli RP-HPLC method geliştirilmiştir ve ICH kılavuzlarına göre valide edilmiştir. Geliştirilen yöntem farklı stres koşullarında Artemether’ in kararlılığını göstermek için kullanılmıştır. Artemether ve bozunma ürünlerinin ayrımı Zorbax Eclipse Plus C18 kolon 250 × 4.6 mm, 5 μm kullanılarak asetonirtil ve su 70:30 karışımı ile 1.0 mL/dak akış hızında 13.48 dakikada gerçekleştirilmiştir. Dedeksiyon, dizi diyot dedektör aracılığıyla 216 nm dalga boyunda gerçekleştirilmiştir ve kolon oda sıcaklığında tutulmuştur. Artemether’in bozunma davranışı stres koşullarında hidroliz, oksidasyon, fotoliz ve termal bozunma uygulanarak incelenmiştir. Düşük sıcaklıklarda 60 °C kararlı olan Artemether için sulu ortamda nötr, asidik, bazik , UV ışık altında ve hidrojen peroksit %3 - %10 ortamında bozunma gözlenmiştir. Geliştirilen valide edilmiş RP-HPLC yöntemi, impürüte profillenmesinde, ilacın kalite kontrolünde, ilaç sanayisinde rutin analizlerde, biyoeşdeğerlik çalışmalarında ve dissolüsyon çalışmalarında kullanılabilir.

Anahtar Kelimeler:

Artemether, Stres Bozundurma Profili, RP-HPLCDAD

Forced Degradation Profiling of Artemether by Validated Stability-Indicating RP-HPLC-DAD Method

A novel stability-indicating RP-HPLC method for artemether has been developed and validated as per ICH guidelines and applied successfully to establish inherent stability of the drug by performing forced degradation in different stress conditions. The chromatographic separation of artemether and its degradants was achieved on Zorbax Eclipse Plus C18 column 250 × 4.6 mm, 5 μm by employing the mixture of acetonitrile and water 70:30 at 13.48 min with 1.0 μL/min flow rate. The detection was performed by photodiode-array detector at 216 nm and room temperature was monitored for column. The degradation behavior drug was determined by performing forced degradation profile viz. hydrolysis, oxidation, photolysis and thermal decomposition. Extensive degradation was found in hydrolytic conditions neutral, acid and alkaline , while it was stable under temperature 60 °C , UV irradiation and in hydrogen peroxide solution 3 and 10% . The validated RP-HPLC-DAD method may be applied for impurity profiling, quality control for purity of drug, routine analysis in pharmaceutical industry, bioequivalence and dissolution studies.

Keywords:

Artemether, Forced degradation profiling, RP-HPLC-DAD,

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