Sacubitril/valsartan was indicated for the treatment of heart failure and hypertension in patients with end-stage renal disease on peritoneal dialysis therapy. Herein, a rapid, sensitive and robust method based on ultra-liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) was developed and validated for the determination of the concentrations of valsartan, sacubitril and its major metabolite LBQ657 in plasma, urine and peritoneal dialysis fluid. Samples were extracted from various biological fluids using protein precipitation. Extracts were subjected to UPLC–MS/MS with electrospray ionization in positive-ion mode. The developed method was fully validated over a concentration range of 8.00–8000 ng/mL for valsartan, 2.00–2000 ng/mL for sacubitril and 30.0–30,000 ng/mL for LBQ657 in plasma, 2.00–1000 ng/mL for valsartan, 1.00–500 ng/mL for sacubitril and 20.0–10000 ng/mL for LBQ657 in urine, and 0.200–100 ng/mL for valsartan, 0.0400–20.0 ng/mL for sacubitril and 2.00–1000 ng/mL for LBQ657 in peritoneal dialysis fluid. The intra- and inter-day precisions for all analytes in various matrices were less than 12.3%, and the intra- and inter-day accuracies results were all between 88.0% and 109.2%. All analytes were stable for at least 8 h at room temperature (25°C), five freeze–thaw cycles, and 37 days at −40°C and −80°C in plasma, urine and peritoneal dialysis fluid. In conclusion, this developed method is reliable, sensitive and specific for determining the concentrations of valsartan, sacubitril and LBQ657 in plasma, urine and peritoneal dialysis fluid. The assay was available to pilot the pharmacokinetics study of sacubitril/valsartan in patients with end-stage renal disease on peritoneal dialysis, and it could provide evidence that peritoneal dialysis had an effect on the clearance of sacubitril/valsartan.

沙库巴曲/缬沙坦适用于接受腹膜透析治疗的终末期肾病患者的心力衰竭和高血压。在此，开发并验证了一种基于超液相色谱-串联质谱 (UPLC-MS/MS) 的快速、灵敏和稳健的方法，用于测定血浆、尿液和尿液中缬沙坦、沙库巴曲及其主要代谢物 LBQ657 的浓度。腹膜透析液。使用蛋白质沉淀从各种生物体液中提取样品。提取物在正离子模式下进行 UPLC-MS/MS 电喷雾电离。所开发的方法在 8.00–8000 ng/mL 的缬沙坦浓度范围、2.00–2000 ng/mL 的 sacubitril 和 30.0–30,000 ng/mL 血浆中的 LBQ657、2.00–1000 ng/mL 的缬沙坦浓度范围内得到了充分验证，1 . 腹膜透析中沙库巴曲 00–500 ng/mL 和 LBQ657 20.0–10000 ng/mL，缬沙坦 0.200–100 ng/mL，沙库巴曲 0.0400–20.0 ng/mL 和 LBQ657 2.00–1000 ng/mL体液。各种基质中所有分析物的日内和日间精度均小于12.3%，日内和日间精度结果均在88.0%~109.2%之间。所有分析物在室温（25°C）、5 个冻融循环下至少 8 小时稳定，在血浆、尿液和腹膜透析液中在 -40°C 和 -80°C 下稳定 37 天。总之，这种开发的方法对于测定血浆、尿液和腹膜透析液中缬沙坦、沙库巴曲和 LBQ657 的浓度是可靠、灵敏和特异的。