Citation: Veera Raghava Raju THUMMALA, Mohana Krishna LANKA. Development and validation of a stability-indicating reverse phase ultra performance liquid chromatographic method for the estimation of nebivolol impurities in active pharmaceutical ingredients and pharmaceutical formulation[J]. Chinese Journal of Chromatography, ;2015, 33(10): 1051-1058. doi: 10.3724/SP.J.1123.2015.04043 shu

Development and validation of a stability-indicating reverse phase ultra performance liquid chromatographic method for the estimation of nebivolol impurities in active pharmaceutical ingredients and pharmaceutical formulation

Veera Raghava Raju THUMMALA ^1,2,, ,
Mohana Krishna LANKA ²

1.
1. Analytical Research and Development, Integrated Product Development, Dr. Reddy's Laboratories Ltd., Bachupally, Hyderabad 500072, India;

Corresponding author: Veera Raghava Raju THUMMALA,
Received Date: 24 April 2015

A sensitive, stability-indicating gradient reverse phase ultra performance liquid chromatographic method has been developed for the quantitative estimation of nebivolol impurities in active pharmaceutical ingredient (API) and pharmaceutical formulation. Efficient chromatographic separation was achieved on an Acquity BEH C18 column (100 mm×2.1 mm, 1.7 [WTBZ]μ[WTB4]m) with mobile phase of a gradient mixture. The flow rate of the mobile phase was 0.18 mL/min with column temperature of 30 ℃ and detection wavelength of 281 nm. The relative response factor values of (R^*)-2-(benzylamino)-1-((S^*)-6-fluorochroman-2-yl)ethanol ((R^*S^*) NBV-1), (R)-1-((R)-6-fluorochroman-2-yl)-2-((S)-2-((S)-6-fluoro-chroman-2-yl)-2-hydroxyethylamino)ethanol ((RRSS) NBV-3), 1-(chroman-2-yl)-2-(2-(6-fluorochroman-2-yl)-2-hydroxy ethyl amino)ethanol (monodesfluoro impurity), (S)-1-((R)-6-fluorochroman-2-yl)-2-((R)-2((S)-6-fluoro-chroman-2-yl)-2-hydroxyethylamino)ethanol hydrochloride ((RSRS) NBV-3) and (R^*)-1-((S^*)-6-fluorochroman-2-yl)-2-((S^*)-2-((S^*)-6-fluoro-chroman-2-yl)-2-hydroxyethylamino) ethanol ((R^*S^*S^*S^*) NBV-2) were 0.65, 0.91, 0.68, 0.92 and 0.91 respectively. Nebivolol formulation sample was subjected to the stress conditions of acid, base, oxidative, hydrolytic, thermal, humidity and photolytic degradation. Nebivolol was found to degrade significantly under peroxide stress condition. The degradation products were well resolved from nebivolol and its impurities. The peak purity test results confirmed that the nebivolol peak was homogenous and pure in all stress samples and the mass balance was found to be more than 98%, thus proving the stability-indicating power of the method. The developed method was validated according to International Conference on Hormonization (ICH) guidelines with respect to specificity, linearity, limits of detection and quantification, accuracy, precision and robustness.
- reverse phase ultra performance liquid chromatography
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