Sacubitril–valsartan (SV) is a first-in-class inhibitor of the angiotensin II receptor and neprilysin for the treatment of chronic heart failure (HF) and hypertension. A stereoselective normal-phase high performance liquid chromatographic method was developed and validated for separation of sacubitril (SA), valsartan (VA) and their stereoisomeric impurities. Chromatography was performed using mobile phase A of n-hexane with 0.1% TFA added and mobile phase B comprising ethanol, isopropanol and TFA (80 : 20 : 0.1, v/v/v) and delivered at a flow rate of 1.0 mL min⁻¹ on a Chiralcel OJ-H column (250 mm × 4.6 mm, 5 μm). The stereoisomers were monitored at a wavelength of 254 nm and the whole separation was achieved within 50 min. The method was validated in terms of specificity, linearity (R² ≥ 0.998), accuracy (98.3–99.5%), precision (%RSD ≤ 1.82), limit of detection (0.06 μg mL⁻¹ and 0.10 μg mL⁻¹) and limit of quantification (0.2 μg mL⁻¹ and 0.3 μg mL⁻¹). The sample solution and mobile phase were found to be stable for at least 48 hours. The final optimized method was successfully applied to separate sacubitril–valsartan from their stereoisomers and showed characteristics of good repeatability and accuracy for quantitative determination of the stereoisomers in bulk drug.

中文翻译：

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液相色谱法分离sa草定-缬沙坦及其立体异构体杂质

Sacubitril–valsartan（SV）是血管紧张素II受体和中性溶酶的首批抑制剂，可用于治疗慢性心力衰竭（HF）和高血压。建立了立体选择性正相高效液相色谱方法，并进行了沙奎特利（SA），缬沙坦（VA）及其立体异构体杂质的分离验证。色谱法使用的流动相A进行Ñ己烷，含0.1％TFA溶液，流动相B包含乙醇，异丙醇和TFA（80：20：0.1，V / V / V），并以1.0毫升min的流速输送^{- 1}在Chiralcel OJ-H色谱柱上（250 mm×4.6 mm，5μm）。在254 nm的波长下监测立体异构体，并在50分钟内完成整个分离。该方法已通过特异性，线性（[R ² ≥0.998），准确性（98.3-99.5％），精密（％RSD 1.82≤），检测限（0.06微克毫升^-1和0.10微克毫升^-1）和定量（0.2的极限微克毫升^-1和0.3 μgmL ^-1）。发现样品溶液和流动相在至少48小时内稳定。最终的优化方法已成功应用于将沙比特比尔-缬沙坦与立体异构体分离的方法，并显示出良好的重复性和准确性，可用于定量测定散装药物中的立体异构体。