title: Investigating the degradation of the sympathomimetic drug phenylephrine by electrospray ionisation-mass spectrometry.
abstract: The frequently used sympathomimetic drug phenylephrine has been studied by electrospray ionisation-mass spectrometry. The stability of the adrenoceptor agonist was examined by investigations of the pharmaceutically used salts phenylephrine hydrochloride and phenylephrine bitartrate. Photostability has been studied by use of an irradiation equipment emitting a solar radiation spectrum. The experiments were carried out by analysis of aqueous drug solutions before and after irradiation treatment. The phenylephrine derivative with unsaturated side chain originating from the drug by loss of one water molecule has been detected as the major degradation product of both phenylephrine salts the hydrochloride and the bitartrate. Further degradation and oxidation products were detectable already in the full scan mode demonstrating a low stability of the drug. Tandem mass spectrometry and multiple stage mass spectrometry experiments enabled the establishment of fragmentation schemes of both salts for the first time. Irradiation treatment indicated that phenylephrine bitartrate is more prone to degradation than the hydrochloride because of an additional decomposition sensitivity of the tartaric acid counter ion. An interaction between phenylephrine and its counter ion degradation products via a nucleophilic addition mechanism is suggested to be the explanation for the detected ion signals after irradiation treatment of phenylephrine bitartrate.
authors.affiliation: Martin-Luther-University Halle-Wittenberg, School of Pharmacy, Institute of Pharmaceutics and Biopharmaceutics, Wolfgang-Langenbeck-Strasse 4, D-06120 Halle, Saale, Germany. hagen.trommer@pharmazie.uni-halle.de
authors.forename: Hagen
authors.initials: H
authors.lastname: Trommer
authors.forename: Klaus
authors.initials: K
authors.lastname: Raith
authors.forename: Reinhard H H
authors.initials: RH
authors.lastname: Neubert
mesh_terms: D004355:Drug Stability; D013058:Mass Spectrometry; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010656:Phenylephrine / Q000032:analysis* / Q000737:chemistry*; D055668:Photochemical Processes / Q000528:radiation effects; D012996:Solutions; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013056:Spectrophotometry, Ultraviolet; D013566:Sympathomimetics / Q000032:analysis* / Q000737:chemistry*; D053719:Tandem Mass Spectrometry; D014867:Water / Q000737:chemistry
chemical_list: D012996:Solutions; D013566:Sympathomimetics; D014867:Water; D010656:Phenylephrine