title: Structural characterization of a degradation product of rocuronium using nanoelectrospray-high resolution mass spectrometry.
abstract: Rocuronium bromide is a non-depolarizing neuromuscular blocking agent that causes rapid muscle relaxation after intravenous injection. Regulatory authorities for registration of pharmaceuticals for human use require the evaluation of the stability of active compounds under various stress conditions. Forced degradation of rocuronium bromide was performed under hydrolytic, thermal, photolytic, and oxidative settings. HPLC-UV/vis analysis revealed an unknown degradation product under oxidative conditions (1% H2 O2 , reflux for 1 h). Investigation of the respective HPLC fraction by high resolution mass spectrometry indicated a formal loss of CH2 and an addition of one oxygen atom to the intact drug molecule. Additional multistage mass spectrometric structural elucidation experiments aided by complementary information from analysis of the intact drug and known rocuronium-related compounds showed that the morpholine moiety was unstable under oxidative stress. The data demonstrated that the morpholine ring was opened and transformed to an N-ethanoyl-formamide group. The structure was supported by appropriate mechanistic explanations.
authors.affiliation: hameln rds GmbH, 31789, Hameln, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Wegener
authors.affiliation: hameln rds GmbH, 31789, Hameln, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Harms
authors.affiliation: Institute of Bioanalytical Chemistry, Saarland University, 66123, Saarbrücken, Germany.
authors.forename: Dietrich A
authors.initials: DA
authors.lastname: Volmer
authors.affiliation: Institute for Inorganic and Analytical Chemistry, University of Münster, 48149, Münster, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Hayen
mesh_terms: D000732:Androstanols / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D006868:Hydrolysis; D003473:Neuromuscular Nondepolarizing Agents / Q000737:chemistry*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010782:Photolysis; D000077123:Rocuronium; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D000077123:Rocuronium
keywords: degradation product; high resolution mass spectrometry; oxidative stress; rocuronium bromide