title: A simpler sampling interface of venturi easy ambient sonic-spray ionization mass spectrometry for high-throughput screening enzyme inhibitors.
abstract: High-throughput screening (HTS) is often required in enzyme inhibitor drugs screening. Mass spectrometry (MS) provides a powerful method for high-throughput screening enzyme inhibitors because its high speed, sensitivity and property of lable free. However, most of the MS methods need complicated sampling interface system. Overall throughput was limited by sample loading in these cases. In this study, we develop a simple interface which coupled droplet segmented system to a venturi easy ambient sonic-spray ionization mass spectrometer. It is fabricated by using a single capillary to act as both sampling probe and the emitter, which simplifies the construction, reduces the cost and shorten the sampling time. Samples sucked by venturi effect are segmented to nanoliter plugs by air, then the plugs can be detected by MS directly. This system eliminated the need for flow injection which was popular used in classic scheme. The new system is applied to screen angiotensin converting enzyme inhibitors. High-throughput was achieved in analyzing 96 samples at 1.6 s per sample. The plugs formation was at 0.5s per sample. Carry-over between samples was less than 5%, the peak height RSD was 2.92% (n = 15). Dose-response curves of 3 known inhibitors were also measured to validate its potential in drug discovery. The calculated IC50 agreed well with reported values.
authors.affiliation: National Institutes for Food and Drug Control, Beijing, 100050, PR China; College of Chemistry, Beijing Normal University, Beijing 100875, PR China; China Pharmaceutical University, Nanjing, 211100, PR China.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: National Institutes for Food and Drug Control, Beijing, 100050, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Chemistry, Beijing Normal University, Beijing 100875, PR China.
authors.forename: YuHan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: National Institutes for Food and Drug Control, Beijing, 100050, PR China. Electronic address: helan1961@aliyun.com.
authors.forename: Lan
authors.initials: L
authors.lastname: He
authors.affiliation: College of Chemistry, Beijing Normal University, Beijing 100875, PR China. Electronic address: jinoyang@bnu.edu.cn.
authors.forename: Jin
authors.initials: J
authors.lastname: Ouyang
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000032:analysis*; D057166:High-Throughput Screening Assays; D013058:Mass Spectrometry / Q000295:instrumentation* / Q000379:methods*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors
keywords: Angiotensin converting enzyme inhibitors; High-throughput screening; Sampling interface; Venturi easy ambient sonic-spray ionization mass spectrometry