Development and validation of a streamlined HPLC-UV method for nitrosamine impurity profiling in sumatriptan tablets and nasal sprays

Abstract

Abstract

Abstract Nitrosamine impurities pose a significant risk to pharmaceutical safety due to their well-documented mutagenic and carcinogenic properties. While these impurities have been detected in various drug products, their presence in sumatriptan (SUMT)–an anti-migraine medication–has not been previously reported. This study aimed to develop and validate a simple, HPLC-UV method for quantifying five nitrosamine impurities in SUMT tablets and nasal spray. These impurities were Nitroso-N-methyl-4-aminobutyric acid (NMBA), N-nitrosodiisopropylamine (NDIPA), N-nitrosodibutyl amine (NDBA), N-nitrosodimethylamine (NDMA), and N-nitrosodiethylamine (NDEA). A new HPLC-UV method was optimized using a single mobile-phase system composed of phosphate buffer (pH 6.0), acetonitrile, and methanol containing 0.1% triethylamine, delivered by programmed gradient elution and pumped through a C18 Column. The method was fully validated in accordance with the International Council for Harmonization (ICH) guidelines. Chromatographic separation of SUMT and its impurities was efficiently achieved using the specified mobile phase gradient. This method ensured complete resolution of all target compounds within a total analysis time of no more than 30 min, demonstrating rapidity, reliability, and suitability for routine analytical applications. The method exhibited excellent Linearity ( R 2 ≥ 0.9997) over the concentration range of 5–1,000 ng mL −1 . The limits of detection and quantitation were 1.62–6.23 ng mL −1 and 4.89–20 ng mL −1 , respectively. Recovery rates were consistent, with values of ≥91%, with acceptable precision as the relative standard deviations of ≤9.99%. The method was applied to the analysis of commercial tablets and nasal spray formulations for the detection and quantification of nitrosamine impurities. Notably, none of the tested formulation samples contained detectable levels of the nitrosamine impurities. The developed method is a robust, sensitive, and convenient approach for routine monitoring of nitrosamine impurities in SUMT formulations, ensuring compliance with regulatory safety standards.