title: Monitoring binding affinity between drug and α1-acid glycoprotein in real time by Venturi easy ambient sonic-spray ionization mass spectrometry.
abstract: A new approach for monitoring the binding affinity between drugs and alpha 1-acid glycoprotein in real time was developed based on a combination of drug-protein reaction followed by Venturi easy ambient sonic-spray ionization mass spectrometry determination of the free drug concentrations. A known basic drug, propranolol was used to validate the new built method. Binding constant values calculated by venturi easy ambient sonic-spray ionization mass spectrometry was in good accordance with a traditional ultrafiltration combined with high performance liquid chromatography method. Then six types of basic drugs were used as the samples to conduct the real time analysis. Upon injection of alpha 1-acid glycoprotein to the drug mixture, the ion chromatograms were extracted to show the changes in the free drug concentrations in real time. By observing the drop-out of six types of drugs during the whole binding reaction, the binding affinities of different drugs were distinguished. A volume shift validating experiment and an injection delay correcting experiment were also performed to eliminate extraneous factors and verify the reliability of our experiment. Therefore, the features of Venturi easy ambient sonic-spray ionization mass spectrometry (V-EASI-MS) and the experimental results indicate that our technique is likely to become a powerful tool for monitoring drug-AGP binding affinity in real time.
authors.affiliation: Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China; National Institutes for Food and Drug Control, Beijing 100050, China; China Pharmaceutical University, Nanjing 211100, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: National Institutes for Food and Drug Control, Beijing 100050, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Lu
authors.affiliation: Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.
authors.forename: YuHan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.
authors.forename: Chen Xi
authors.initials: CX
authors.lastname: Yao
authors.affiliation: National Institutes for Food and Drug Control, Beijing 100050, China.
authors.forename: BaoMing
authors.initials: B
authors.lastname: Ning
authors.affiliation: Key laboratory for Cell Proliferation and Regulation Biology, Ministry of Education, Beijing Normal University, Beijing 100857, China.
authors.forename: Dacheng
authors.initials: D
authors.lastname: He
authors.affiliation: National Institutes for Food and Drug Control, Beijing 100050, China. Electronic address: helan1961@aliyun.com.
authors.forename: Lan
authors.initials: L
authors.lastname: He
authors.affiliation: Key Laboratory of Theoretical and Computational Photochemistry, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China. Electronic address: jinoyang@bnu.edu.cn.
authors.forename: Jin
authors.initials: J
authors.lastname: Ouyang
mesh_terms: D002851:Chromatography, High Pressure Liquid; D009961:Orosomucoid / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D011485:Protein Binding; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D009961:Orosomucoid; D004364:Pharmaceutical Preparations
keywords: Alpha 1-acid glycoprotein; Binding affinity; Real-time online analysis; Venturi easy ambient sonic-spray ionization