VER（Vericiguat）是一种治疗症状性慢性心力衰竭（HF）的新型可溶性鸟苷酸环化酶激动剂，也是P-糖蛋白和乳腺癌耐药蛋白（BCRP）的底物。Astragaloside IV（ASIV）是黄芪（Radix Astragali）的主要活性成分，是中国广泛用于HF治疗的传统中药。虽然观察到ASIV对P-糖蛋白和BCRP蛋白表达的影响，但其对VER代谢的影响尚不明确。在本研究中，雄性Sprague-Dawley大鼠被给予20 mg/kg的ASIV和1 mg/kg的VER，以研究它们的药代动力学。血样经液液萃取处理，利用替硝苯磺胺作为内标（IS）。分析方法采用C18柱（XSelect® HSS T3柱，2.1 × 100 mm，2.5 μm），流动相为0.1%甲酸和乙腈进行梯度洗脱。流动相的流速设置为0.2 mL/min，每个样品使用5 µL进行分析。通过正离子多反应监测模式，VER的转变质量/电荷比为m/z 427.4→109.1，内标的转变质量/电荷比为m/z 423.3→109.1。该方法在浓度范围为0.1至300 ng/mL内线性良好（r = 0.9987），并且所有验证过程均按照生物分析要求进行。药代动力学结果显示，ASIV对VER的主要参数没有显著影响，仅Cmax下降了33.2%（P < 0.05）。总的来说，我们的研究成功建立了一种选择性、敏感和可重复的超高效液相色谱-质谱联用（UPLC-MS/MS）方法，用于检测大鼠血浆中的VER。版权所有 © 2023 Elsevier B.V. 发表。

Vericiguat (VER) is a novel soluble guanylate cyclase stimulator treating symptomatic chronic heart failure (HF), and it is a substrate of both transporters P-glycoprotein and breast cancer resistance protein (BCRP). Astragaloside IV (ASIV) is the main active ingredient in Radix Astragali (Huangqi), a traditional Chinese medicine widely used for HF treatment in China. ASIV's effect on the protein expression of P-glycoprotein and BCRP has been observed, its impact on VER metabolism remain uncertain. In the present study, male Sprague-Dawley rats were administered with 20 mg/kg ASIV and 1 mg/kg VER to study their pharmacokinetics. Blood samples were subject to liquid-liquid extraction, and riociguat was employed as the internal standard (IS). The analytical method involved a C18 column (XSelect® HSS T3 column, 2.1 × 100 mm, 2.5 μm) with a mobile phase of 0.1% formic acid and acetonitrile for gradient elution. The flow rate of the mobile phase was set at 0.2 mL/min, and 5 µL of the sample was used for analysis. The positive ion multi-response monitoring mode was utilized with a transition of m/z 427.4→109.1 for VER and m/z 423.3→109.1 for the IS. The method exhibited good linearity within the concentration range of 0.1 to 300 ng/mL (r = 0.9987), and all the validation processes were conducted in accordance with the requirements of biological analysis. The pharmacokinetic results revealed that ASIV did not significantly alter the main parameters of VER, except for Cmax, which decreased by 33.2% (P < 0.05). Overall, our study successfully established a selective, sensitive and repeatable ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis for detecting VER in rat plasma.Copyright © 2023. Published by Elsevier B.V.