Abstract

The present study provides a systematic quality by design-based development of a sensitive and rapid liquid chromatographic method coupled with mass spectrometry for the estimation of Riociguat in its formulations. Separation was achieved using the mobile phase of 0.1% formic acid and acetonitrile in the ratio of 10:90 v/v at the flow rate of 1.0 ml/minute using Zorbax C18 column (50 mm × 4.6 mm × 5 μm). The acetonitrile percentage, flow rate, and heat block temperature were identified as critical method parameters and were optimized using central composite design. The obtained model was found to be statistically significant with a probability (p) value of less than 0.05 and the optimized model had composite desirability of 0.826. The method performance was evaluated as per ICH guidelines with linearity ranging from 0.5 to 110 ng/ml, with a correlation coefficient of 0.9995. The detection and quantification limits were 0.1 and 0.5 ng/ml, respectively. The mean recovery was in the range of 98.1%–101.8%.

Key words: LC-MS/MS; Central composite design; Riociguat; Formulations