An accurate and sensitive UPLC–MS/MS method was developed and validated for the simultaneous estimation of the newly developed combination of sacubitril and valsartan and the co-administered drugs nebivolol, chlorthalidone and esomeprazole in human plasma. Solid-phase extraction was conducted for the purification and extraction of the drugs from human plasma. Chromatographic separation was carried out on an Agilent SB-C₁₈ (1.8 μm, 2.1 × 50 mm) column using losartan as internal standard. Isocratic elution was applied using acetonitrile–0.1% formic acid in water (85: 15, v/v) as mobile phase. Detection was carried out using a triple-quadrupole tandem mass spectrometer using multiple reaction monitoring, at positive mode at m/z 412.23 → 266.19 for sacubitril, m/z 436.29 → 235.19 for valsartan, m/z 405.8 → 150.98 for nebivolol, m/z 346.09 → 198 for esomeprazole and a selected combination of two fragments m/z 423.19 → 207.14 and 423.19 → 192.2 for losartan (internal standard), and in negative ionization mode at m/z 337.02 → 190.12 for chlorthalidone. The method was linear over the concentration ranges 30–2,000 ng/ml for sacubitril, 70–2,000 ng/ml for valsartan, esomeprazole and chlorthalidone and 70–5,000 pg/ml for nebivolol. The developed method is sensitive and selective and could be applied for dose adjustment, bioavailability and drug–drug interaction studies.

中文翻译：

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使用固相萃取通过 UPLC-MS/MS 方法同步测定人血浆中沙库巴曲和缬沙坦与一些共同给药的药物

开发并验证了一种准确且灵敏的 UPLC-MS/MS 方法，用于同时评估新开发的沙库巴曲和缬沙坦组合以及共同给药的药物奈必洛尔、氯噻酮和埃索美拉唑在人血浆中的含量。固相萃取用于从人血浆中纯化和提取药物。在 Agilent SB-C ₁₈（1.8 μm，2.1 × 50 mm）色谱柱上使用氯沙坦作为内标进行色谱分离。使用乙腈-0.1% 甲酸水溶液 (85: 15, v/v) 作为流动相进行等度洗脱。使用三重四极杆串联质谱仪使用多反应监测进行检测，在正模式下，沙库巴曲m/z 412.23 → 266.19，m/z缬沙坦为 436.29 → 235.19，奈必洛尔m/z 405.8 → 150.98，埃索美拉唑m/z 346.09 → 198 以及两个片段的选定组合m/z 423.19 → 207.19 → 207.14 和 41923 → 阴性标准品（2 标准品中的m/z 423.19 → 207.19 → 阴性）离子化模式在m / z 337.02 → 190.12 氯噻酮。该方法在沙库巴曲 30–2,000 ng/ml、缬沙坦、埃索美拉唑和氯噻酮 70–2,000 ng/ml 和奈必洛尔 70–5,000 pg/ml 的浓度范围内呈线性。所开发的方法具有灵敏性和选择性，可用于剂量调整、生物利用度和药物-药物相互作用研究。