title: Ultra high performance supercritical fluid chromatography coupled with tandem mass spectrometry for screening of doping agents. I: Investigation of mobile phase and MS conditions.
abstract: The conditions for the analysis of selected doping substances by UHPSFC-MS/MS were optimized to ensure suitable peak shapes and maximized MS responses. A representative mixture of 31 acidic and basic doping agents was analyzed, in both ESI+ and ESI- modes. The best compromise for all compounds in terms of MS sensitivity and chromatographic performance was obtained when adding 2% water and 10mM ammonium formate in the CO2/MeOH mobile phase. Beside mobile phase, the nature of the make-up solvent added for interfacing UHPSFC with MS was also evaluated. Ethanol was found to be the best candidate as it was able to compensate for the negative effect of 2% water addition in ESI- mode and provided a suitable MS response for all doping agents. Sensitivity of the optimized UHPSFC-MS/MS method was finally assessed and compared to the results obtained in conventional UHPLC-MS/MS. Sensitivity was improved by 5-100-fold in UHPSFC-MS/MS vs. UHPLC-MS/MS for 56% of compounds, while only one compound (bumetanide) offered a significantly higher MS response (4-fold) under UHPLC-MS/MS conditions. In the second paper of this series, the optimal conditions for UHPSFC-MS/MS analysis will be employed to screen >100 doping agents in urine matrix and results will be compared to those obtained by conventional UHPLC-MS/MS.
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Nováková
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Boulevard d'Yvoy 20, 1211 Geneva 4, Switzerland.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Grand-Guillaume Perrenoud
authors.affiliation: Swiss Laboratory for Doping Analyses, University Centre of Legal Medicine, West Switzerland, Chemin des Croisettes 22, 1066 Epalinges, Switzerland.
authors.forename: Raul
authors.initials: R
authors.lastname: Nicoli
authors.affiliation: Swiss Laboratory for Doping Analyses, University Centre of Legal Medicine, West Switzerland, Chemin des Croisettes 22, 1066 Epalinges, Switzerland.
authors.forename: Martial
authors.initials: M
authors.lastname: Saugy
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Boulevard d'Yvoy 20, 1211 Geneva 4, Switzerland.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Veuthey
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Boulevard d'Yvoy 20, 1211 Geneva 4, Switzerland. Electronic address: davy.guillarme@unige.ch.
authors.forename: Davy
authors.initials: D
authors.lastname: Guillarme
mesh_terms: D002245:Carbon Dioxide / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards; D025924:Chromatography, Supercritical Fluid / Q000379:methods* / Q000592:standards; D004300:Doping in Sports; D006863:Hydrogen-Ion Concentration; D007477:Ions / Q000737:chemistry; D000432:Methanol / Q000737:chemistry; D058573:Performance-Enhancing Substances / Q000032:analysis* / Q000592:standards; D012015:Reference Standards; D053719:Tandem Mass Spectrometry / Q000379:methods* / Q000592:standards; D014867:Water / Q000737:chemistry
chemical_list: D007477:Ions; D058573:Performance-Enhancing Substances; D014867:Water; D002245:Carbon Dioxide; D000432:Methanol
keywords: Doping agents; Make-up solvent; Mobile phase; Ultra high performance liquid chromatography; Ultra high performance supercritical fluid chromatography