Ultra high performance supercritical fluid chromatography coupled with tandem mass spectrometry for screening of doping agents. II: Analysis of biological samples Lucie Nováková a , Marco Rentsch b , Alexandre Grand-Guillaume Perrenoud c , Raul Nicoli d , Martial Saugy d , Jean-Luc Veuthey c , Davy Guillarme c, * a Department of Analytical Chemistry, Faculty of Pharmacy, Charles University in Prague, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic b Waters AG, Taefernstrasse 4, 5405 Baden-Daetwill, Switzerland c School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, Boulevard D'Yvoy 20, 1211 Geneva 4, Switzerland d Swiss Laboratory for Doping Analyses, University Center of Legal Medicine, West Switzerland, Chemin des Croisettes 22, 1066 Epalinges, Switzerland H I G H L I G H T S G R A P H I C A L A B S T R A C T  110 doping agents were tested in UHPLC–MS/MS and UHPSFC–MS/MS.  Urine matrix was successfully ana- lyzed in UHPSFC–MS/MS.  Higher sensitivity was achieved in UHPSFC–MS/MS for 32% of the com- pounds.  UHPSFC–MS/MS was less susceptible to matrix effects than UHPLC–MS/ MS.  UHPSFC–MS/MS can be considered for the screening of doping agents, as an alternative to UHPLC–MS/MS. A R T I C L E I N F O Article history: Received 6 June 2014 Received in revised form 26 August 2014 Accepted 6 October 2014 Available online 13 October 2014 Keywords: Ultra high performance supercritical fluid chromatography Ultra high performance liquid chromatography Doping agents Biological samples Urine Matrix effects A B S T R A C T The potential and applicability of UHPSFC–MS/MS for anti-doping screening in urine samples were tested for the first time. For this purpose, a group of 110 doping agents with diverse physicochemical properties was analyzed using two separation techniques, namely UHPLC–MS/MS and UHPSFC–MS/MS in both ESI+ and ESI modes. The two approaches were compared in terms of selectivity, sensitivity, linearity and matrix effects. As expected, very diverse retentions and selectivities were obtained in UHPLC and UHPSFC, proving a good complementarity of these analytical strategies. In both conditions, acceptable peak shapes and MS detection capabilities were obtained within 7 min analysis time, enabling the application of these two methods for screening purposes. Method sensitivity was found comparable for 46% of tested compounds, while higher sensitivity was observed for 21% of tested compounds in UHPLC– MS/MS and for 32% in UHPSFC–MS/MS. The latter demonstrated a lower susceptibility to matrix effects, which were mostly observed as signal suppression. In the case of UHPLC–MS/MS, more serious matrix effects were observed, leading typically to signal enhancement and the matrix effect was also concentration dependent, i.e., more significant matrix effects occurred at the lowest concentrations. ã 2014 Elsevier B.V. All rights reserved. * Corresponding author. Tel.: +41 22 379 34 63; fax: +41 22 379 68 08. E-mail address: davy.guillarme@unige.ch (D. Guillarme). http://dx.doi.org/10.1016/j.aca.2014.10.007 0003-2670/ ã 2014 Elsevier B.V. All rights reserved. Analytica Chimica Acta 853 (2015) 647–659 Contents lists available at ScienceDirect Analytica Chimica Acta journa l home page : www.e lsevier.com/loca te/aca