色谱

色谱 ›› 2015, Vol. 33 ›› Issue (10): 1051-1058.DOI: 10.3724/SP.J.1123.2015.04043

• 研究论文 • 上一篇    下一篇

指示稳定性的反相超高效液相色谱评价原料药和制剂配方中奈必洛尔杂质的方法建立与验证(英文)

Veera Raghava Raju THUMMALA1,2, Mohana Krishna LANKA2   

  1. 1. Analytical Research and Development, Integrated Product Development, Dr. Reddy's Laboratories Ltd., Bachupally, Hyderabad 500072, India;
    2. School of Chemistry, Andhra University, Visakhapatnam 530003, A. P., India
  • 收稿日期:2015-04-24 出版日期:2015-10-08 发布日期:2012-05-09
  • 通讯作者: Veera Raghava Raju THUMMALA

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 THUMMALA1,2, Mohana Krishna LANKA2   

  1. 1. Analytical Research and Development, Integrated Product Development, Dr. Reddy's Laboratories Ltd., Bachupally, Hyderabad 500072, India;
    2. School of Chemistry, Andhra University, Visakhapatnam 530003, A. P., India
  • Received:2015-04-24 Online:2015-10-08 Published:2012-05-09

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摘要：

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.

关键词: impurities, International Conference on Hormonization (ICH) guidelines, nebivolol, stability-indicating, reverse phase ultra performance liquid chromatography

Abstract:

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.

Key words: impurities, International Conference on Hormonization (ICH) guidelines, nebivolol, reverse phase ultra performance liquid chromatography, stability-indicating

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