Sacubitril (SBT) is a neprilysin inhibitor, approved by food and drug administration (FDA) in 2015, under the FDA’s priority review process. In this work, we report the validated stability indicating method of SBT by employing quality by design (QbD) principles related to analytical method development, capable in separation of 11 impurities. Chromatographic separation was performed on an ascentis phenyl hexyl column using 10 mM KH₂PO₄ as a mobile phase-A and the pH adjusted to 2.1. Methanol: acetonitrile (70:30 v/v) solvent mixture was employed as the mobile phase-B in a gradient mode of elution at a flow rate 0.8 mL/min at 30°C. The column effluents were monitored by a photo diode array detector set at a wavelength of maximum absorption 254 nm noted for all the impurities and furthermore for SBT. This method was remarked to be accurate in the range from 92 to 116%, precise with relative standard deviation 0.9% for SBT (0.8 mg/mL) and 1.0 to 2.1% for its related impurities (0.0005 mg/mL) also linear with correlation coefficient r ≥ 0.9989. The limits of quantification for all impurities were 0.05% with respect to sample concentration 0.8 mg/mL. The developed method revealed a good method operable design range for the experimental chromatographic conditions. Forced degradation of SBT carried under acidic, basic and oxidative stressed conditions manifested that the method is stability indicating.

中文翻译：

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质量通过设计方法开发出稳定性指示方法，以通过高效液相色谱对沙必比尔的相关物质和降解产物进行定量。

Sacubitril（SBT）是一种neprilysin抑制剂，在FDA的优先审查程序下，于2015年被食品和药物管理局（FDA）批准。在这项工作中，我们通过采用与分析方法开发相关的设计质量（QbD）原理，报告了经过验证的SBT稳定性指示方法，该方法能够分离11种杂质。色谱分离是在Ascentis苯基己基色谱柱上使用10 mM KH ₂ PO _4进行的作为流动相-A，pH调节至2.1。甲醇：乙腈（70:30 v / v）溶剂混合物以梯度洗脱方式在30°C以0.8 mL / min的流速用作流动相B. 通过设置为最大吸收254 nm的波长的光电二极管阵列检测器监测柱流出物，对于所有杂质，还对SBT记录该波长。该方法的准确度为92％至116％，相对标准偏差（SBT（0.8 mg / mL）为0.9％，相关杂质（0.0005 mg / mL）为1.0至2.1％）也呈线性关系系数r ≥0.9989。相对于样品浓度0.8 mg / mL，所有杂质的定量限为0.05％。所开发的方法揭示了针对实验色谱条件的良好方法可操作设计范围。在酸性，碱性和氧化应激条件下进行的SBT的强制降解表明该方法具有稳定性。