Bortezomib Enjeksiyonluk Çözeltileri İçin Stabilite Göstergeli UHPLC Yöntemlerinin Geliştirilmesi ve Validasyonu

Öz

Enjekte edilebilir formülasyonlarda bortezomibin kantitatif tayini için hızlı ve sağlam bir stabilite belirleyici Ultra Yüksek Performanslı Sıvı Kromatografisi (UHPLC) yöntemi geliştirilmiş ve valide edilmiştir. Yöntemde, fosfat tamponu ve asetonitril kullanılarak gradyan elüsyonlu bir C18 kolon kullanılmış ve kısa bir çalışma süresi içinde optimum ayırma sağlanmıştır. Doğrusallık, 2-10 mg/mL konsantrasyon aralığında R² > 0,999 ile doğrulanmıştır. Yöntem, ICH Q2(R2) yönergelerine uygun olarak doğrulanmış ve özgüllük, kesinlik, doğruluk, sağlamlık ve çözelti kararlılığı göstermiştir. Asidik, bazik, oksidatif, termal ve fotolitik stres altında zorla bozunma çalışmaları, yöntemin bortezomibi bozunma ürünlerinden kabul edilebilir kütle dengesi ile ayırabildiğini doğrulamıştır. Geliştirilen yöntem, bortezomib enjeksiyon çözeltilerinin rutin kalite kontrol ve stabilite analizleri için uygundur.

Anahtar Kelimeler

• Analitik yöntem validasyonu
• Bortezomib
• bozunma çalışması
• UHPLC
• stabilite
• zorlu bozunma

Development and validation of stability-indicating UHPLC methods for bortezomib injection solutions

Öz

A rapid and robust stability-indicating Ultra-High-Performance Liquid Chromatography (UHPLC) method was developed and validated for the quantitative determination of bortezomib in injectable formulations. The method employed a C18 column with gradient elution using a phosphate buffer and acetonitrile, achieving optimal separation within a short runtime. Linearity was confirmed across the concentration range of 2–10 mg/mL with R² > 0.999. The method was validated in accordance with ICH Q2(R2) guidelines, demonstrating specificity, precision, accuracy, robustness, and solution stability. Forced degradation studies under acidic, basic, oxidative, thermal, and photolytic stress confirmed that the method is capable of separating bortezomib from its degradation products with acceptable mass balance. The developed method is suitable for routine quality control and stability analysis of bortezomib injection solutions.

Anahtar Kelimeler

• Analytical method validation
• Bortezomib
• degradation study
• ; UHPLC
• stability
• forced degradation

Kaynakça

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