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
We report that 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:
-
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Chemical Sciences Division
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1257832
- Alternate Identifier(s):
- OSTI ID: 1496293
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Journal of Pharmaceutical and Biomedical Analysis
- Additional Journal Information:
- Journal Volume: 100; Journal Issue: C; Journal ID: ISSN 0731-7085
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; 38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY; 3,4,3-LI(1,2-HOPO) ligand; LC-MSMS; structural elucidation; method development; fragmentation
Citation Formats
Panyala, Nagender R., Sturzbecher-Hoehne, Manuel, and Abergel, Rebecca J. 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. United States: N. p., 2014.
Web. doi:10.1016/j.jpba.2014.08.004.
Panyala, Nagender R., Sturzbecher-Hoehne, Manuel, & Abergel, Rebecca J. 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. United States. https://doi.org/10.1016/j.jpba.2014.08.004
Panyala, Nagender R., Sturzbecher-Hoehne, Manuel, and Abergel, Rebecca J. Tue .
"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". United States. https://doi.org/10.1016/j.jpba.2014.08.004. https://www.osti.gov/servlets/purl/1257832.
@article{osti_1257832,
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},
author = {Panyala, Nagender R. and Sturzbecher-Hoehne, Manuel and Abergel, Rebecca J.},
abstractNote = {We report that 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.},
doi = {10.1016/j.jpba.2014.08.004},
journal = {Journal of Pharmaceutical and Biomedical Analysis},
number = C,
volume = 100,
place = {United States},
year = {Tue Aug 12 00:00:00 EDT 2014},
month = {Tue Aug 12 00:00:00 EDT 2014}
}
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Works referenced in this record:
Medical Countermeasures against Nuclear Threats: Radionuclide Decorporation Agents
journal, October 2008
- Cassatt, David R.; Kaminski, Joseph M.; Hatchett, Richard J.
- Radiation Research, Vol. 170, Issue 4
Lauriston s. Taylor Lecture: the Quest for Therapeutic Actinide Chelators
journal, January 2008
- Durbin, Patricia W.
- Health Physics, Vol. 95, Issue 5
Biomimetic Actinide Chelators: an Update on the Preclinical Development of the Orally Active Hydroxypyridonate Decorporation Agents 3,4,3-Li(1,2-Hopo) and 5-Lio(Me-3,2-Hopo)
journal, January 2010
- Abergel, Rebecca J.; Durbin, Patricia W.; Kullgren, Birgitta
- Health Physics, Vol. 99, Issue 3
Dose-Dependent Efficacy and Safety Toxicology of Hydroxypyridinonate Actinide Decorporation Agents in Rodents: Towards a Safe and Effective Human Dosing Regimen
journal, February 2013
- Bunin, Deborah I.; Chang, Polly Y.; Doppalapudi, Rupa S.
- Radiation Research, Vol. 179, Issue 2
Significance of Single Variables in Defining Adequate Animal Models to Assess the Efficacy of New Radionuclide Decorporation Agents: Using the Contamination Dose as an Example: Animal Models for Chelating Agents Efficacy
journal, August 2012
- Jarvis, Erin E.; An, Dahlia D.; Kullgren, Birgitta
- Drug Development Research, Vol. 73, Issue 5
Actinide chelation: biodistribution and in vivo complex stability of the targeted metal ions
journal, October 2012
- Kullgren, Birgitta; Jarvis, Erin E.; An, Dahlia D.
- Toxicology Mechanisms and Methods, Vol. 23, Issue 1
Synthesis of 3,4,3 LI 1,2 HOPO labelled with 14C: Synthesis of 3,4,3
journal, February 2001
- Burgada, R.; Bailly, T.; Noël, J. P.
- Journal of Labelled Compounds and Radiopharmaceuticals, Vol. 44, Issue 1, p. 13-19
Ferric ion sequestering agents. 13. Synthesis, structures, and thermodynamics of complexation of cobalt(III) and iron(III) tris complexes of several chelating hydroxypyridinones
journal, March 1985
- Scarrow, Robert C.; Riley, Paul E.; Abu-Dari, Kamal
- Inorganic Chemistry, Vol. 24, Issue 6
Specific sequestering agents for the actinides. 16. Synthesis and initial biological testing of polydentate oxohydroxypyridinecarboxylate ligands
journal, January 1988
- White, David L.; Durbin, Patricia W.; Jeung, Nylan
- Journal of Medicinal Chemistry, Vol. 31, Issue 1, p. 11-18
Gadolinium complex of tris[(3-hydroxy-1-methyl- 2-oxo-1,2-didehydropyridine-4-carboxamido)ethyl]-amine: A New Class of gadolinium magnetic resonance relaxation agents
journal, July 1995
- Xu, Jide; Franklin, Sonya J.; Whisenhunt, Donald W.
- Journal of the American Chemical Society, Vol. 117, Issue 27, p. 7245-7246
Specific Sequestering Agents for the Actinides. 28. Synthesis and Initial Evaluation of Multidentate 4-Carbamoyl-3-hydroxy-1-methyl-2(1H)-pyridinone Ligands for in Vivo Plutonium(IV) Chelation
journal, July 1995
- Xu, Jide; Kullgren, Birgitta; Durbin, Patricia W.
- Journal of Medicinal Chemistry, Vol. 38, Issue 14
Applications of hyphenated LC-MS techniques in pharmaceutical analysis
journal, January 2000
- Ermer, Joachim; Vogel, Martin
- Biomedical Chromatography, Vol. 14, Issue 6
A multidisciplinary approach to identify a degradation product in a pharmaceutical dosage form
journal, March 2011
- Pan, Changkang; Guan, Jack; Lin, Melissa
- Journal of Pharmaceutical and Biomedical Analysis, Vol. 54, Issue 4
Simvastatin: Review of Updates on Recent Trends in Pharmacokinetics, Pharmacodynamics, Drug–drug Interaction, Impurities and Analytical Methods
journal, May 2012
- Kumar Basniwal, Pawan; Jain, Deepti
- Current Pharmaceutical Analysis, Vol. 8, Issue 2
A critical review on the use of modern sophisticated hyphenated tools in the characterization of impurities and degradation products
journal, October 2012
- Singh, Saranjit; Handa, Tarun; Narayanam, Mallikarjun
- Journal of Pharmaceutical and Biomedical Analysis, Vol. 69
Identification and characterization of process related impurities in chloroquine and hydroxychloroquine by LC/IT/MS, LC/TOF/MS and NMR
journal, May 2009
- Dongre, Vaijanath G.; Ghugare, Pradeep D.; Karmuse, Pravin
- Journal of Pharmaceutical and Biomedical Analysis, Vol. 49, Issue 4
Isolation and structural identification of an impurity in fluconazole bulk drug substance
journal, November 2007
- Dongre, Vaijanath G.; Ghugare, Pradeep D.; Karmuse, Pravin P.
- Journal of Pharmaceutical and Biomedical Analysis, Vol. 45, Issue 3
Characterization and quantitative determination of impurities in piperaquine phosphate by HPLC and LC/MS/MS
journal, January 2007
- Dongre, Vaijanath G.; Karmuse, Pravin P.; Ghugare, Pradeep D.
- Journal of Pharmaceutical and Biomedical Analysis, Vol. 43, Issue 1
Investigation of amodiaquine bulk drug impurities by liquid chromatography/ion trap mass spectrometry
journal, July 2008
- Dongre, Vaijanath G.; Karmuse, Pravin P.; Ghugare, Pradip D.
- Rapid Communications in Mass Spectrometry, Vol. 22, Issue 14
Solution-phase deuterium/hydrogen exchange at a specific residue using nozzle-skimmer and electron capture dissociation mass spectrometry
journal, January 2006
- Hagman, Charlotte; Tsybin, Yury O.; Håkansson, Per
- Rapid Communications in Mass Spectrometry, Vol. 20, Issue 4
Combination of nozzle-skimmer fragmentation and partial acid hydrolysis in electrospray ionization time-of-flight mass spectrometry of synthetic peptides
journal, June 1998
- Håkansson, Kristina; Zubarev, Roman; Håkansson, Per
- Rapid Communications in Mass Spectrometry, Vol. 12, Issue 11
Shotgun Sequencing Small Oligonucleotides by Nozzle-Skimmer Dissociation and Electrospray Ionization Mass Spectrometry
journal, April 2005
- Meng, Zhaojing; Limbach, Patrick A.
- European Journal of Mass Spectrometry, Vol. 11, Issue 2
New developments in biochemical mass spectrometry: electrospray ionization
journal, May 1990
- Smith, Richard D.; Loo, Joseph A.; Edmonds, Charles G.
- Analytical Chemistry, Vol. 62, Issue 9
Consecutive Ion Activation for Top Down Mass Spectrometry: Improved Protein Sequencing by Nozzle−Skimmer Dissociation
journal, September 2005
- Zhai, Huili; Han, Xuemei; Breuker, Kathrin
- Analytical Chemistry, Vol. 77, Issue 18
In-source fragmentation and accurate mass analysis of multiclass flavonoid conjugates by electrospray ionization time-of-flight mass spectrometry
journal, April 2011
- Abrankó, László; García-Reyes, Juan F.; Molina-Díaz, Antonio
- Journal of Mass Spectrometry, Vol. 46, Issue 5
Distinction of theC-glycosylflavone isomer pairs orientin/isoorientin and vitexin/isovitexin using HPLC-MS exact mass measurement and in-source CID
journal, January 2005
- Pereira, Cíntia A. M.; Yariwake, Janete H.; McCullagh, Michael
- Phytochemical Analysis, Vol. 16, Issue 5
A Pseudo MS3 Approach for Identification of Disulfide-Bonded Proteins: Uncommon Product Ions and Database Search
journal, December 2011
- Chen, Jianzhong; Shiyanov, Pavel; Schlager, John J.
- Journal of The American Society for Mass Spectrometry, Vol. 23, Issue 2
Using the Antenna Effect as a Spectroscopic Tool: Photophysics and Solution Thermodynamics of the Model Luminescent Hydroxypyridonate Complex [Eu III (3,4,3-LI(1,2-HOPO))] −
journal, December 2009
- Abergel, Rebecca J.; D’Aléo, Anthony; Ng Pak Leung, Clara
- Inorganic Chemistry, Vol. 48, Issue 23
Development of a Practical Synthesis of Toll-like Receptor Agonist PF-4171455: 4-Amino-1-benzyl-6-trifluoromethyl-1,3-dihydroimidazo [4,5- c ] pyridin-2-one
journal, July 2011
- Adam, Fiona M.; Bish, Gerwyn; Calo, Frederick
- Organic Process Research & Development, Vol. 15, Issue 4
Works referencing / citing this record:
Quinquennial Review of Progress in Degradation Studies and Impurity Profiling: An Instrumental Perspective Statistics
journal, May 2019
- Shelke, Madhav; Deshpande, Shirish Shriram; Sharma, Sanjay
- Critical Reviews in Analytical Chemistry, Vol. 50, Issue 3