title: A Sensitive Dilute-and-Shoot Approach for the Simultaneous Screening of 71 Stimulants and 7 Metabolites in Human Urine by LC-MS-MS with Dynamic MRM.
abstract: A novel, reliable and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed with dynamic multiple reaction monitoring (dMRM) mode for the simultaneous screening of 71 stimulants and 7 metabolites in human urine using unsophisticated MS instruments (Agilent triple-quadruple 6410 B mass spectrometer). With a known retention time of an analyte, dMRM algorithm monitors each MRM transition only around its expected retention time. Therefore, dMRM enables the maximization of dwell times and provides much higher sensitivity and reproducibility than the conventional multiple reaction monitoring mode (cMRM). After precipitation of protein, the urine sample was injected into LC-MS-MS system directly without sample pre-concentration. For comparison, cMRM and dMRM acquisitions were performed under the same chromatographic conditions. The result showed that the signal response and quality of the chromatograms for each stimulant improved significantly with dMRM over cMRM. The method has been fully validated giving limits of detection (0.1-25 ng/mL) satisfactory for its application to anti-doping analysis. The repeatability of the concentrations and the retention times are good both for intra- and for inter-day experiments (%CV of concentrations always <20 and %CV of retention times <0.5). The method also afforded satisfactory results in terms of accuracy, matrix effect and specificity.
authors.affiliation: National Anti-Doping Laboratory, China Anti-Doping Agency, 1st Anding Road, Chaoyang District, Beijing 100029, P. R. China dongying@chinada.cn.
authors.forename: Ying
authors.initials: Y
authors.lastname: Dong
authors.affiliation: National Anti-Doping Laboratory, China Anti-Doping Agency, 1st Anding Road, Chaoyang District, Beijing 100029, P. R. China.
authors.forename: Kuan
authors.initials: K
authors.lastname: Yan
authors.affiliation: National Anti-Doping Laboratory, China Anti-Doping Agency, 1st Anding Road, Chaoyang District, Beijing 100029, P. R. China.
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Ma
authors.affiliation: National Anti-Doping Laboratory, China Anti-Doping Agency, 1st Anding Road, Chaoyang District, Beijing 100029, P. R. China.
authors.forename: Shan
authors.initials: S
authors.lastname: Wang
authors.affiliation: National Anti-Doping Laboratory, China Anti-Doping Agency, 1st Anding Road, Chaoyang District, Beijing 100029, P. R. China.
authors.forename: Genye
authors.initials: G
authors.lastname: He
authors.affiliation: National Anti-Doping Laboratory, China Anti-Doping Agency, 1st Anding Road, Chaoyang District, Beijing 100029, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Deng
authors.affiliation: National Anti-Doping Laboratory, China Anti-Doping Agency, 1st Anding Road, Chaoyang District, Beijing 100029, P. R. China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000697:Central Nervous System Stimulants / Q000378:metabolism* / Q000652:urine*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004300:Doping in Sports; D006801:Humans; D057230:Limit of Detection; D015203:Reproducibility of Results; D015813:Substance Abuse Detection / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000697:Central Nervous System Stimulants