Karglumik Asit Tablet Ürünü İçin Kromatografik Teknikler Kullanılarak Bozunma Ürünleri Tayin Metodu Geliştirilmesi Ve Validasyonu

Abstract

Carglumic acid (N-carbamoyl-L-glutamic acid) is a critical pharmaceutical agent used in the treatment of hyperammonaemia associated with urea cycle disorders and organic acidemias. In this study, highly accurate and sensitive analytical methods were developed, optimized, and validated in accordance with ICH Q2(R2) guidelines for the quantification, dissolution testing, and impurity profiling of carglumic acid in tablet formulations. For dissolution and assay analyses, an HPLC-DAD method was developed using a reversedphase C18 column and a mobile phase composed of phosphate buffer and acetonitrile. Detection was performed at 205 nm. The method exhibited linearity over the range of 0.5–60 μg/mL (R² > 0.999), with accuracy within 98–102% and precision with relative standard deviations (RSD) below 2%. A UHPLC-DAD method was developed for impurity profiling, enabling the reliable detection and separation of low-level degradation products. The method was optimized using Box- Behnken design for critical parameters such as pH, column temperature, and flow rate. Robustness was evaluated using the Plackett-Burman design. Stress degradation studies confirmed the method’s stability-indicating capability. Dissolution tests were performed under physiologically relevant conditions (pH 1.2, 4.5, and 6.8), and over 90% drug release was observed within 15 minutes. Filtration and solution stability studies supported the suitability of the analytical conditions. The developed HPLC-DAD and UHPLC-DAD methods demonstrated high selectivity, reproducibility, and sensitivity, making them reliable analytical tools for pharmaceutical quality control and stability evaluation of carglumic acid formulations.