An LC–tandem mass spectrometry method was developed and validated for the simultaneous quantitation of fimasartan and sacubitrilat using positive ion mode. The protein precipitation method was employed for the extraction of fimasartan, sacubitrilat and alprazolam (internal standard) from rat heparinized plasma. Baseline separation of the analytes was accomplished using an ACE‐5, C₁₈ (4.6 × 50 mm) column and gradient elution of mobile phase A (5 mm ammonium formate and 0.1% formic acid in purified water) and B (acetonitrile:methanol, 80:20; v/v). All peaks of interest were eluted within a 5‐min runtime. The quantitation was achieved in the selected reaction monitoring mode. The developed method was validated as per US Food and Drug Administration guidelines and met the pre‐defined acceptance criteria. The method showed linearity from 5 to 10,000 ng/mL. The accuracy/precision of intra‐ and inter‐batch assays was 96.64%/2.05% to 109.17%/13.70% and 100.74%/3.76% to 106.39%/9.75% for fimasartan and 100.02%/1.49% to 113.80%/9.38% and 100.75%/2.31% to 108.40%/7.74% for sacubitrilat, respectively, in rat plasma. Fimasartan and sacubitrilat remained stable in rat plasma at different experimental conditions up to 21 days. The developed method was sensitive, selective and applied successfully to monitor plasma concentrations of fimasartan and sacubitrilat in an oral rat pharmacokinetic study.

中文翻译：

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三重四极杆液相色谱-串联质谱法同时使用电喷雾电离以正模式同时测定大鼠血浆中的糖精和Fimasartan

液相色谱串联质谱法已开发并验证了使用正离子模式同时定量测定菲马沙坦和ac糖的效果。蛋白质沉淀法用于从大鼠肝素化血浆中提取fimasartan，sacubitrilat和alprazolam（内标）。使用ACE-5，C ₁₈（4.6×50 mm）色谱柱和流动相A（5 m m甲酸铵和纯水中的0.1％甲酸）和B（乙腈：甲醇，80:20; v / v）。所有感兴趣的峰在5分钟的运行时间中被洗脱。在选定的反应监测模式下完成定量。所开发的方法已按照美国食品和药物管理局的指导原则进行了验证，并且符合预定的接受标准。该方法的线性范围为5至10,000 ng / mL。批内和批间分析的准确性/精密度分别为96.64％/ 2.05％至109.17％/ 13.70％和菲马沙坦为100.74％/ 3.76％至106.39％/ 9.75％和100.02％/ 1.49％至113.80％/ 9.38％在大鼠血浆中，糖囊藻分别为100.75％/ 2.31％至108.40％/ 7.74％。在不同实验条件下，至21天，Fimasartan和sacubitrilat在大鼠血浆中均保持稳定。开发的方法很敏感，