A stability-indicating and environmentally sustainable UPLC method for simultaneous determination of rizatriptan, meloxicam, and related N-nitrosamine impurities

Abstract

A robust and sensitive ultra-performance liquid chromatography (UPLC) method was developed and rigorously validated for the simultaneous quantification of rizatriptan, meloxicam, and their corresponding N-nitrosamine impurities in pharmaceutical dosage forms. Method development and optimization were conducted using a Box–Behnken Design to systematically investigate the effects of acetonitrile proportion, mobile phase flow rate, and pH on critical chromatographic responses, including retention time and tailing factor. Optimal separation was achieved with a mobile phase comprising 30 % v/v acetonitrile, a flow rate of 0.2 mL/min, and a pH of 2.5, resulting in well-resolved, symmetrical peaks. Validation performed in accordance with ICH guidelines confirmed excellent linearity (R² > 0.999) over the tested concentration ranges, low limits of detection (0.47–1.39 µg/mL), high precision (%RSD <2 %), and satisfactory accuracy (98–102 % recoveries). The method demonstrated robustness under deliberate minor variations of chromatographic parameters and maintained specificity by effectively resolving target analytes from degradation products during forced degradation studies. Sustainability and environmental impact were comprehensively assessed using ComplexGAPI, AGREE, AGREEprep, Analytical Eco-Scale, and Blue Applicability Grade Index metrics, all indicating high greenness and operational suitability. Application of the method to the commercial combination product Symbravo confirmed its capability for accurate quantification of active pharmaceutical ingredients and low-level nitrosamine impurities. Collectively, these findings underscore the method’s suitability for routine quality control, impurity profiling, and regulatory compliance in modern pharmaceutical analysis.