title: Micellar electrokinetic chromatography-electrospray ionization mass spectrometry for the identification of drug impurities.
abstract: Previously, we have presented a system hyphenating continuous micellar electrokinetic chromatography (MEKC) with electrospray ionization mass spectrometry (ESI-MS). Here we evaluate this technique for its applicability in impurity profiling of drugs using galantamine and ipratropium as test samples. A background electrolyte (BGE) of 10mM sodium phosphate (pH 7.5), 12.5-15% acetonitrile and 20mM sodium dodecylsulfate (SDS) was used for the MEKC-MS analysis of a galantamine sample containing a number of related impurities, and a heat-treated solution of ipratropium containing a number of unknown degradation products. MEKC provided efficient separation of all sample constituents. Despite the presence of non-volatile BGEs, all impurities in the galantamine sample could be detected by ESI-MS in their respective extracted ion traces (XICs) with a detection sensitivity in the sub-microg/ml range (full-scan mode). MS/MS detection provided useful product spectra allowing the structural characterization of the respective galantamine impurities. With the MEKC-MS/MS system, two degradation products could be revealed and identified in the heat-stressed ipratropium sample. The presented method shows good potential for the detection and structure elucidation of minor impurities in drug substances.
authors.affiliation: Department of Biomedical Analysis, Utrecht University, P.O. Box 80082, 3508 TB Utrecht, The Netherlands.
authors.forename: Roelof
authors.initials: R
authors.lastname: Mol
authors.forename: Else
authors.initials: E
authors.lastname: Kragt
authors.forename: Ilias
authors.initials: I
authors.lastname: Jimidar
authors.forename: Gerhardus J
authors.initials: GJ
authors.lastname: de Jong
authors.forename: Govert W
authors.initials: GW
authors.lastname: Somsen
mesh_terms: D020374:Chromatography, Micellar Electrokinetic Capillary / Q000379:methods*; D004340:Drug Contamination; D005702:Galantamine / Q000032:analysis*; D009241:Ipratropium / Q000032:analysis*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry; D014466:Ultraviolet Rays
chemical_list: D005702:Galantamine; D009241:Ipratropium