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 C max , 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.
Nourhan M. Amaar,Fathi S. Awad,Wael I. Mortada,A.B. Abdallah
An innovative imprinted electrochemical platform was designed for the first time to detect vericiguat (VER), a soluble guanylate cyclase stimulator, in real samples. The smart sensor was fabricated by mixing a molecularly imprinted polymer (MIP) with graphite powder, obtained from a broken battery, and multiwalled carbon nanotubes (MWCNT) in the presence of paraffin oil. Density functional theory (DFT) was utilized not only to predict promising monomers for the polymerization process but also to investigate the interaction between the selected monomers and the VER template. Highly interactive acrylamide and methyl methacrylate monomers were first employed to interact with the VER template; then, the initiator, 2,2′-azobisisobutyronitrile, and the cross linker, ethylene glycol dimethacrylate, were added. The resulting MIP was characterized using different techniques including Fourier transform infrared spectroscopy, atomic force microscopy, scanning electron microscopy, and elemental mapping. The electrochemical performance of the synthesized sensor was investigated using cyclic voltammetry and electrochemical impedance spectroscopy. Using differential pulse voltammetry, the fabricated imprinted sensor was successfully utilized to monitor VER with a low limit of detection of 1.68 × 10 −9 mol L −1 over a linear concentration range of 5.1 × 10 −9 mol L −1 –2.3 × 10 −4 mol L −1 , with a correlation coefficient of 0.98. In addition, it showed excellent selectivity in the presence of other coexisting molecules, high stability (32 days), and good reproducibility (RSD = 4.68 %) and repeatability (RSD = 3.86 %). The proposed technique was successfully employed to detect VER in real blood samples and pharmaceutical tablets with quantitative extraction recovery (99.40 %–100.05 %).
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