Nitrosamine impurities, including N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA), are classified as genotoxic and carcinogenic. Their occurrence in pharmaceuticals, even at trace levels, necessitates sensitive analytical methods. Palaveratone, a steroidal active pharmaceutical ingredient, requires rigorous monitoring for these impurities. This study aimed to develop and validate a simple, reliable and sensitive RP-HPLC method for the quantification of NDMA and NDEA in palaveratone, following ICH Q2(R1) and ICH M7(R1) guidelines. Chromatographic separation was performed on a Platisil C18 column (250 × 4.6 mm, 5 µm) with an isocratic mobile phase of potassium dihydrogen phosphate buffer and acetonitrile (10:90 v/v). The flow rate was 1.0 mL/min, detection wavelength 296 nm and injection volume 20 µL. The method was validated for specificity, linearity, precision, accuracy, detection limit (DL) and quantitation limit (QL). NDMA and NDEA were well resolved without interference. The DL and QL were 0.035 ppm and 0.093 ppm, respectively. Linearity was excellent (R² = 0.999), recoveries ranged from 98.2–115.2% and precision studies yielded %RSD values <6%. Intermediate precision met the cumulative acceptance limit of ≤20.0. The validated method was found sensitive, accurate and reproducible, making it suitable for routine quality control and regulatory compliance of nitrosamine impurities in palaveratone.
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