title: SFC-MS/MS as an orthogonal technique for improved screening of polar analytes in anti-doping control.
abstract: HPLC is considered the method of choice for the separation of various classes of drugs. However, some analytes are still challenging as HPLC shows limited resolution capabilities for highly polar analytes as they interact insufficiently on conventional reversed-phase (RP) columns. Especially in combination with mass spectrometric detection, limitations apply for alterations of stationary phases. Some highly polar sympathomimetic drugs and their metabolites showed almost no retention on different RP columns. Their retention remains poor even on phenylhexyl phases that show different selectivity due to π-π interactions. Supercritical fluid chromatography (SFC) as an orthogonal separation technique to HPLC may help to overcome these issues. Selected polar drugs and metabolites were analyzed utilizing SFC separation. All compounds showed sharp peaks and good retention even for the very polar analytes, such as sulfoconjugates. Retention times and elution orders in SFC are different to both RP and HILIC separations as a result of the orthogonality. Short cycle times could be realized. As temperature and pressure strongly influence the polarity of supercritical fluids, precise regulation of temperature and backpressure is required for the stability of the retention times. As CO2 is the main constituent of the mobile phase in SFC, solvent consumption and solvent waste are considerably reduced. Graphical Abstract SFC-MS/MS vs. LC-MS/MS.
authors.affiliation: Institute of Pharmacy, Freie Universität Berlin, Koenigin-Luise-Str. 2-4, 14195, Berlin, Germany. maria.parr@fu-berlin.de.
authors.forename: Maria Kristina
authors.initials: MK
authors.lastname: Parr
authors.affiliation: Agilent Technologies, 5301 Stevens Creek Boulevard, Santa Clara, CA, 95051, USA.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Wuest
authors.affiliation: Agilent Technologies, 5301 Stevens Creek Boulevard, Santa Clara, CA, 95051, USA.
authors.forename: Edgar
authors.initials: E
authors.lastname: Naegele
authors.affiliation: Institute of Pharmacy, Freie Universität Berlin, Koenigin-Luise-Str. 2-4, 14195, Berlin, Germany.
authors.forename: Jan F
authors.initials: JF
authors.lastname: Joseph
authors.affiliation: Institute of Pharmacy, Freie Universität Berlin, Koenigin-Luise-Str. 2-4, 14195, Berlin, Germany.
authors.forename: Maxi
authors.initials: M
authors.lastname: Wenzel
authors.affiliation: Institute of Pharmacy, Freie Universität Berlin, Koenigin-Luise-Str. 2-4, 14195, Berlin, Germany.|Chromicent GmbH, Rudower Chaussee 29, 12489, Berlin, Germany.
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Schmidt
authors.affiliation: Chromicent GmbH, Rudower Chaussee 29, 12489, Berlin, Germany.
authors.forename: Mijo
authors.initials: M
authors.lastname: Stanic
authors.affiliation: Laboratorio Antidoping FMSI, Largo Giulio Onesti 1, 00197, Rome, Italy.
authors.forename: Xavier
authors.initials: X
authors.lastname: de la Torre
authors.affiliation: Laboratorio Antidoping FMSI, Largo Giulio Onesti 1, 00197, Rome, Italy.|Department of Experimental Medicine, 'Sapienza' University of Rome, Viale Regina Elena 324, 00161, Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Botrè
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000652:urine; D001993:Bronchodilator Agents / Q000378:metabolism / Q000652:urine; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D025924:Chromatography, Supercritical Fluid / Q000379:methods*; D004300:Doping in Sports; D005280:Fenoterol / Q000378:metabolism / Q000652:urine; D006801:Humans; D057230:Limit of Detection; D004364:Pharmaceutical Preparations / Q000378:metabolism / Q000652:urine*; D011433:Propranolol / Q000378:metabolism / Q000652:urine; D015813:Substance Abuse Detection / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000319:Adrenergic beta-Antagonists; D001993:Bronchodilator Agents; D004364:Pharmaceutical Preparations; D005280:Fenoterol; D011433:Propranolol
keywords: Beta-blockers; Dilute-and-inject; Doping control; Polar stimulants; Sulfoconjugates; Sympathomimetic drugs