Swaim Leigh L, Johnson Rudolph C, Zhou Yingtao, Sandlin Chris, Barr John R
Centers for Disease Control and Prevention, National Center for Environmental Health, Division of Laboratory Sciences, Emergency Response and Air Toxicants Branch, 4770 Buford Highway, MS F44, Atlanta, Georgia 30341, USA.
J Anal Toxicol. 2008 Nov-Dec;32(9):774-7. doi: 10.1093/jat/32.9.774.
A reduced-volume, high-throughput analytical method has been developed for the quantification of organophosphorus (OP) nerve agent metabolites in human urine. Metabolites of soman, sarin, cyclohexyl-sarin, VX, and Russian-VX were quantified down to a lowest reportable limit of 1 ng/mL in human urine. One hundred microliter urine samples were preconcentrated using normal-phase 96-well solid-phase extraction silica sorbent beds. Dual-column hydrophilic interaction liquid chromatography was applied in a 2.5-min isocratic separation followed by negative electrospray isotope-dilution multiple-reaction-monitoring mass spectrometry. Method validation included the characterization of two synthetic urine pools, relative recovery experiments, and calculation of the method limit of detection. All liquid handling steps were processed in a high-density 96-well format, including sample aliquoting, extraction, dry-down, and reconstitution. This allows up to 3840 unknown samples, plus calibrators and quality control materials, to be prepared on a single liquid handler in a 24-h period. In a public health emergency involving OP-nerve agents, this method provides the sample preparation and analytical capacity to respond rapidly to a large number of patient samples.
已开发出一种体积减小、高通量的分析方法，用于定量测定人尿中的有机磷（OP）神经毒剂代谢物。梭曼、沙林、环己基沙林、VX和俄罗斯-VX的代谢物在人尿中的最低可报告限量定量至1 ng/mL。使用正相96孔固相萃取硅胶吸附剂床对100微升尿样进行预浓缩。采用双柱亲水相互作用液相色谱法进行2.5分钟等度分离，随后进行负电喷雾同位素稀释多反应监测质谱分析。方法验证包括对两个合成尿样池的表征、相对回收率实验以及方法检测限的计算。所有液体处理步骤均以高密度96孔形式进行，包括样品分装、萃取、干燥和复溶。这使得在24小时内，一台液体处理仪上最多可制备3840个未知样品以及校准品和质量控制材料。在涉及OP神经毒剂的突发公共卫生事件中，该方法提供了对大量患者样品做出快速反应的样品制备和分析能力。
