Synthesis and Characterization and Anticoagulant Properties of Diethyl Citrate

Abstract

Anticoagulation is an essential for the success of hemodialysis. However, sodium citrate (Na₃Cit), a major anticoagulant in current clinical application, causes hypocalcemia due to its strong binding with Ca²⁺ ion and the slow Ca²⁺ release rate from the chelate formed. We have synthesized a novel anticoagulant: diethyl citrate (Et₂Cit). The compound was charcterized by its elemental analysis, infrared spectroscopy, mass spectrometry and nuclear magnetic resonance. The purity was established by thin layer chromatography and acid titration. The mass fraction of Et₂Cit was 99.27 %. The in vitro anticoagulatory effect of Et₂Cit was investigated by measuring the whole blood activated clotting time. Since the introduction of two ethyl groups to citric acid enhanced the steric hindrance for Ca²⁺ chelation, it led to a reduced Ca²⁺ chelation and accelerated Ca²⁺ release from Et₂Cit in comparison to Na₃Cit. Acute toxicity test in mice shows that Et₂Cit has no serious risk of acute poisoning. Therefore, Et₂Cit can be a potential and an ideal anticoagulant.