Simultaneous Enrichment and Ultrasensitive Detection of Angiotensin I, II, and III and Aldosterone in Human Plasma Based on Magnetic Covalent Organic Frameworks and LC-MS/MS

Abstract

Angiotensin I, II, and III (Ang I, II, and III) and aldosterone (Aldo) play an important role in primary aldosteronism (PA) screening according to the study of the blood pressure regulation mechanism. However, Ang I, Ang II, Ang III, and Aldo are present in human plasma at low concentrations and have different polarities, which make it rather challenging for current detection methods to simultaneously detect four analytes in complex blood samples. In this study, a new magnetic covalent organic framework (COF) was synthesized for the enrichment of Ang I, II, and III and Aldo in human plasma, and a new method for the simultaneous detection of four analytes was developed based on the magnetic COF and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The experimental results demonstrated that the adsorption kinetics of the material conformed to a pseudo-second-order model, and the enrichment mechanisms were π-π stacking, electrostatic, and hydrogen bonding interactions. Under the optimized conditions, the established method has satisfactory linear ranges (Ang I: 100–25,000 pg/mL, Ang II: 2–500 pg/mL, Ang III: 3–750 pg/mL, and Aldo: 20–5000 pg/mL), a low limit of detection (0.8–5 pg/mL), high recoveries (93.0–111.3%), and multiple recycling, which were superior to those reported studies. Meanwhile, the results of testing 20 clinical samples indicated that Ang I, Ang II, Ang III, and Aldo were effective and could be used as new biomarkers for PA screening, which proved the feasibility of enriching the four targets in real blood samples. The prepared magnetic COF in this experiment provided a reference for the material design to simultaneous enrichment of Ang I, Ang II, Ang III, and Aldo, and the developed new method based on the magnetic COF and LC-MS/MS provided a new detection idea for PA screening, which greatly promoted the development of PA disease diagnosis and was expected to be used in further clinical research.