Development and Validation of a Stability-Indicating HPLC Method for the Quantification of Organic Impurities in Drug Product Carglumic Acid Tablets

Developing a robust analytical method for impurity profiling and quality control is essential for carglumic acid, an orphan drug lacking a United States Pharmacopeia (USP) monograph. This study establishes a straightforward, reliable, economical, and rapid high-performance liquid chromatography (HPLC) assay for the quantification of carglumic acid and its associated organic impurities in ۲۰۰ mg oral suspension tablets. The method underwent comprehensive validation per ICH Q۲(R۱) guidelines, assessing specificity, system precision, method precision, precision at the limit of quantification (LOQ), linearity, range, accuracy, robustness, ruggedness, and solution stability. For key impurities, relative retention times (RRTs) and relative response factors (RRFs) were established: pyroglutamic acid at ۷.۸ min, related compound A (RC-A) at ۹.۶ min, and related compound B (RC-B) at ۱۴.۶ min. Linearity was exemplary across a broad dynamic range, from LOQ (۰.۸% of specification) to ۴۰۰%, with robust correlation coefficients. Solution stability testing at ۵°C for ۴۸ hours confirmed minimal variation, with peak area deviations <۲۵%. Specificity was affirmed through forced degradation experiments, revealing no interference from diluent or placebo matrices under acidic, basic, oxidative, thermal, photolytic, and hydrolytic stress conditions. Overall, this validated HPLC method demonstrates high sensitivity, accuracy, precision, and stability-indicating capability, rendering it ideal for routine quality control of carglumic acid tablets. It provides a dependable analytical platform for quality assurance of this vital therapeutic, particularly in the absence of compendial standards.

کلیدواژه ها:

Carglumic Acid ، HPLC ، Method Validation ، Organic Impurities ، Specificity ، Stability indicating