School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.
School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China.
J Pharm Biomed Anal. 2018 Feb 5;149:133-142. doi: 10.1016/j.jpba.2017.11.011. Epub 2017 Nov 4.
Vonoprazan fumarate is a novel potassium-competitive acid blocker for the treatment of acid-related diseases. In the present study, a simple, fast, and economic reversed-phase liquid chromatography (LC) method was developed for the analysis of ten related substances (raw materials, by-products and degradants) in vonoprazan fumarate. The optimized separation was performed on a Phenomenex Kinetex EVO C (250mm×4.6mm, 5.0μm) column. The mobile phase consisted of (A) 0.03M sodium phosphate buffer (pH adjusted to 6.5) - methanol - acetonitrile (72:25:3, v/v/v) and (B) 0.03M sodium phosphate buffer (pH adjusted to 6.5) - acetonitrile (30:70, v/v). Detection of the analytes was conducted at 230nm using a UV detector. The stability-indicating ability of this method was demonstrated by carrying out forced degradation studies. Vonoprazan underwent significant degradation when subjected to alkaline and oxidative stress conditions, while the drug proved to be stable to acidic, thermal and photolytic degradation. The degradants did not interfere with the detection of vonoprazan fumarate and its impurities. The performance of this method was validated in accordance to the regulatory guidelines recommended by the International Conference on Harmonisation (ICH) and this validation included specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision and robustness. The method proposed in this paper could be applied for process development as well as quality assurance of vonoprazan in bulk drug, since no monograph is available in official compendia.
富马酸伏诺拉生是一种新型钾离子竞争性酸阻滞剂，用于治疗酸相关疾病。本研究建立了一种简单、快速、经济的反相高效液相色谱法，用于分析富马酸伏诺拉生中的 10 种有关物质（原料药、副产物和降解产物）。在 Phenomenex Kinetex EVO C （250mm×4.6mm，5.0μm）柱上优化分离条件。流动相由（A）0.03M 磷酸钠缓冲液（pH 调至 6.5）-甲醇-乙腈（72:25:3，v/v/v）和（B）0.03M 磷酸钠缓冲液（pH 调至 6.5）-乙腈（30:70，v/v）组成。采用紫外检测器，在 230nm 处检测分析物。通过强制降解研究证明了该方法的稳定性指示能力。富马酸伏诺拉生在碱性和氧化应激条件下会发生显著降解，而在酸性、热和光降解条件下则稳定。降解产物不干扰富马酸伏诺拉生及其杂质的检测。该方法的性能按照国际人用药品注册技术协调会（ICH）推荐的法规指南进行验证，包括专属性、线性、检测限（LOD）、定量限（LOQ）、准确度、精密度和耐用性。本文所建立的方法可用于富马酸伏诺拉生原料药的工艺开发和质量保证，因为官方药典中尚无专论。
