RP-HPLC KULLANILARAK TASARIM YAKLAŞIMI YOLUYLA KOMBİNE FORMÜLASYONDA BULUNAN LAMİVUDİN VE EFFAVİRENZ’İN TAYİNİNE YÖNELİK YÖNTEM GELİŞTİRİLMESİ

Öz

Amaç: Kombinasyon formülasyonunda lamivudin (LAM) ve effavirenzin (EVZ) ölçümü için karmaşık olmayan ve güvenilir bir sıvı kromatografik yaklaşım önerilmiştir. Gereç ve Yöntem: Deney tasarımı (DoE), RP-HPLC yönteminin çok değişkenli optimizasyonu için deneysel koşulları ayarlamak üzere kullanıldı. RP-HPLC yönteminin çok değişkenli optimizasyonu, deneysel koşullar, deney tasarımı (DoE) kullanılarak gerçekleştirildi. Kritik yöntem parametreleri bir risk değerlendirmesi ile belirlendi. Matematiksel modeller üç bağımsız değişken kullanılarak oluşturulmuştur: asetonitril yüzdesi, metanol yüzdesi ve tampon pH'ı. Bu bağımsız öğelerin etkileri, yanıt yüzeyi metodolojisini analiz etmek için kullanılan merkezi bileşik tasarım (CCD) kullanılarak ayrıntılı bir şekilde incelenmiştir. Sonuç ve Tartışma: LAM ve EVZ tutma süresi ve çözünürlüğü, arzu edilebilirlik işlevi kullanılarak aynı anda optimize edildi. Her biri 40:20:40 v/v oranlarındaki asetonitril, metanol ve fosfat tamponu (pH 7.0), 215 nm'lik bir dalga boyunda meydana gelen algılama ile kontur diyagramından optimize edilmiş ve beklenen verilerde kullanılmıştır. Her iki farmasötik maddenin yüksek çözünürlükte ve 6 dakikanın altında çalışma süresiyle temel ayrımı, bu ideal koşullar altında gerçekleştirildi. Doğrulanmış test parametreleri, ICH önerilerini izledi. Sonuç olarak, bulgular Tasarıma Göre Kalite metodolojisinin LAM ve EVZ'nin eş zamanlı ölçümü için RP-HPLC tekniğini optimize etmek üzere başarılı bir şekilde kullanılabileceğini göstermiştir.

Anahtar Kelimeler

• Effavirenz
• lamivudin
• merkezi kompozit tasarım
• RP-HPLC
• tasarıma göre kalite

UTILITY OF QUALITY BY DESIGN APPROACH IN RP-HPLC METHOD DEVELOPMENT FOR QUANTIFICATION OF LAMIVUDINE AND EFFAVIRENZ IN COMBINATION FORMULATION

Öz

Objective: For the measurement of lamivudine(LAM) and effavirenz (EVZ) in combination formulation, an uncomplicated and reliable liquid chromatographic approach has been proposed. Material and Method: The design of experiments (DoE) was used to set up the experimental conditions for the multivariate optimization of the RP-HPLC method. The crucial method parameters were determined by a risk assessment. The mathematical models were created using three independent variables: percentage of acetonitrile, percentage of methanol, and buffer pH. The impacts of these independent elements were thoroughly investigated using the central composite design (CCD), which was utilized to analyze the response surface methodology. Result and Discussion: The LAM and EVZ retention time and resolution were both concurrently optimized using the desirability function. Acetonitrile, methanol, and phosphate buffer (pH 7.0) in the proportions of 40:20:40 v/v each were used in the optimized and anticipated data from the contour diagram, with detection occurring at a wavelength of 215 nm. Baseline separation of both pharmaceuticals with high resolution and a run time of under 6 minutes was accomplished under these ideal conditions. The validated test parameters followed ICH recommendations. As a consequence, the findings demonstrated that the Quality by Design methodology could be successfully used to optimize the RP-HPLC technique for the concurrent quantification of LAM and EVZ.

Anahtar Kelimeler

• Central composite design
• effavirenz
• lamivudine
• quality by design
• RP-HPLC

Kaynakça

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