title: Identification of process related trace level impurities in the actinide decorporation agent 3,4,3-LI(1,2-HOPO): Nozzle-skimmer fragmentation via ESI LC-QTOFMS.
abstract: 3,4,3-LI(1,2-HOPO) is a chelating ligand and decorporation agent that can remove radioactive lanthanides and actinides from the body. Identification of trace impurities in drug samples is gaining much interest due to their significant influence on drug activity. In this study, trace impurities were detected in manufactured lots of 3,4,3-LI(1,2-HOPO) by a developed method of liquid chromatography coupled with photo-diode array UV detection and electrospray ionization-quadrupole time of flight mass spectrometry (LC-QTOFMS), via induced-in-source or collision-induced mass fragmentation (nozzle-skimmer fragmentation). Molecular ions were fragmented within the nozzle-skimmer region of electrospray ionization (ESI) mass spectrometer equipped with a Time of Flight detector. Eight major (detected at levels higher than a 0.1% threshold) and seven minor trace impurities were identified. The respective structures of these impurities were elucidated via analysis of the generated fragment ions using mass fragmentation and elemental composition software. Proposed structures of impurities were further confirmed via isotopic modeling.
authors.affiliation: Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Nagender R
authors.initials: NR
authors.lastname: Panyala
authors.affiliation: Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Manuel
authors.initials: M
authors.lastname: Sturzbecher-Hoehne
authors.affiliation: Chemical Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address: rjabergel@lbl.gov.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Abergel
mesh_terms: D002614:Chelating Agents / Q000032:analysis*; D002853:Chromatography, Liquid / Q000379:methods*; D004340:Drug Contamination; D006573:Heterocyclic Compounds, 1-Ring / Q000032:analysis*; D008958:Models, Molecular; D015394:Molecular Structure; D011728:Pyridones / Q000032:analysis*; D012984:Software; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013056:Spectrophotometry, Ultraviolet; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: C000594124:1,5,10,14-tetra(1-hydroxy-2-pyridon-6-oyl)-1,5,10,14-tetraazatetradecane; D002614:Chelating Agents; D006573:Heterocyclic Compounds, 1-Ring; D011728:Pyridones
keywords: 3,4,3-LI(1,2-HOPO) ligand; Fragmentation; LC–MS/MS; Method development; Structural elucidation