title: Quantification of electrochemically generated iodine-containing metabolites using inductively coupled plasma mass spectrometry.
abstract: For the risk assessment of drug candidates, the identification and quantification of their metabolites is required. The majority of analytical techniques is based on calibration standards for quantification of the metabolites. As these often are not readily available, the use of inductively coupled plasma mass spectrometry (ICPMS) is an attractive alternative for drugs containing heteroatoms. In this work, the online coupling of electrochemistry (EC), liquid chromatography (LC), and ICPMS is presented. The antiarrhythmic agent amiodarone, which contains two iodine atoms, is oxidized in an electrochemical flow-through cell under N-dealkylation and deiodination. The metabolites that are generated at different EC potentials are identified by electrospray ionization (ESI) mass spectrometry, compared to those from rat liver microsomal incubations and quantified by ICPMS. Phase-optimized LC, a recent approach for high-performance isocratic separations, is used to avoid the ICPMS calibration problems known to occur with gradient separations. The potential of the complementary use of ESI-MS and ICPMS for the qualitative and quantitative analysis of drug metabolites becomes apparent in this work.
authors.affiliation: Institut für Anorganische and Analytische Chemie, Westfälische Wilhelms-Universität Munster, Corrensstrasse 30, 48149 Münster, Germany.
authors.forename: Wiebke
authors.initials: W
authors.lastname: Lohmann
authors.forename: Björn
authors.initials: B
authors.lastname: Meermann
authors.forename: Ines
authors.initials: I
authors.lastname: Möller
authors.forename: Andy
authors.initials: A
authors.lastname: Scheffer
authors.forename: Uwe
authors.initials: U
authors.lastname: Karst
mesh_terms: D000638:Amiodarone / Q000032:analysis* / Q000378:metabolism; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000032:analysis* / Q000378:metabolism; D002853:Chromatography, Liquid; D004563:Electrochemistry; D007455:Iodine / Q000737:chemistry*; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000889:Anti-Arrhythmia Agents; D007455:Iodine; D000638:Amiodarone