title: Pharmaceutical doses of the banned stimulant oxilofrine found in dietary supplements sold in the USA.
abstract: Oxilofrine (4-[1-hydroxy-2-(methylamino)propyl]phenol) is a pharmaceutical stimulant prescribed in dosages of 16 to 40 mg to stimulate the heart and increase blood pressure. It has never been approved for use in the USA as a prescription drug or as a dietary supplement. Several athletes, however, have been banned from sport for testing positive for oxilofrine and have claimed that they inadvertently consumed oxilofrine in sports supplements. Consumption of supplements containing oxilofrine may also pose serious health risks. For example, one brand of supplements containing oxilofrine has been linked to serious adverse events including vomiting, agitation, and cardiac arrest. We designed our study to determine the presence and quantity of oxilofrine in dietary supplements sold in the USA. A validated ultra-high performance liquid chromatography-quadrupole time of flight-mass spectrometry method was developed for the identification and quantification of oxilofrine. The separation was achieved using a reversed phase column, mass spectrometry detection, and a water/acetonitrile gradient as the mobile phase. The presence of oxilofrine was confirmed using a reference standard. We analyzed 27 brands of supplements labelled as containing a synonym of oxilofrine ('methylsynephrine') and found that oxilofrine was present in 14 different brands (52%) at dosages ranging from 0.0003 to 75 mg per individual serving. Of the supplements containing oxilofrine, 43% (6/14) contained pharmaceutical or greater dosages of oxilofrine. Following instructions on the label, consumers could ingest as much as 250 mg of oxilofrine per day. The drug oxilofrine was found in pharmacological and greater dosages in supplements labelled as containing methylsynephrine. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA.|Cambridge Health Alliance, Somerville, MA, 02143, USA.
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Cohen
authors.affiliation: National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.
authors.forename: Bharathi
authors.initials: B
authors.lastname: Avula
authors.affiliation: National Institute for Public Health and the Environment (RIVM), Bilthoven, Netherlands.
authors.forename: Bastiaan
authors.initials: B
authors.lastname: Venhuis
authors.affiliation: NSF International, Ann Arbor, MI, 48105, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Travis
authors.affiliation: National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.
authors.forename: Yan-Hong
authors.initials: YH
authors.lastname: Wang
authors.affiliation: National Center for Natural Products Research, School of Pharmacy, University of Mississippi, University, MS, 38677, USA.
authors.forename: Ikhlas A
authors.initials: IA
authors.lastname: Khan
mesh_terms: D002316:Cardiotonic Agents / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D019587:Dietary Supplements / Q000032:analysis*; D004809:Ephedrine / Q000031:analogs & derivatives* / Q000032:analysis; D013287:Illicit Drugs / Q000032:analysis*; D057230:Limit of Detection; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013578:Synephrine / Q000031:analogs & derivatives / Q000032:analysis
chemical_list: D002316:Cardiotonic Agents; D013287:Illicit Drugs; C026055:oxilofrine; D004809:Ephedrine; D013578:Synephrine
keywords: UHPLC-QToF-MS; dietary supplements; hydroxyephedrine; methylsynephrine; oxilofrine