High Mass Analysis with a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer: From Inorganic Salt Clusters to Antibody Conjugates and Beyond

Campuzano, Iain D.  G.; Nshanian, Michael; Spahr, Christopher; Lantz, Carter; Netirojjanakul, Chawita; Li, Huilin; Wongkongkathep, Piriya; Wolff, Jeremy J.; Loo, Joseph A.

doi:10.1021/jasms.0c00030

Title: High Mass Analysis with a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer: From Inorganic Salt Clusters to Antibody Conjugates and Beyond

Journal Article · Fri Mar 20 00:00:00 EDT 2020 · Journal of the American Society for Mass Spectrometry

DOI:https://doi.org/10.1021/jasms.0c00030· OSTI ID:1799611

^[1]; Nshanian, Michael ^[2]; Spahr, Christopher ^[1]; Lantz, Carter ^[2]; Netirojjanakul, Chawita ^[1];

^[2]; Wongkongkathep, Piriya ^[2]; Wolff, Jeremy J. ^[3];

^[2]

Amgen Inc., Thousand Oaks, CA (United States)
Univ. of California, Los Angeles, CA (United States)
Bruker Daltonics Inc, Billerica, MA (United States)

Analysis of proteins and complexes under native mass spectrometric (MS) and solution conditions was typically performed using time-of-flight (ToF) analyzers, due to their routine high m/z transmission and detection capabilities. However, over recent years, the ability of Orbitrap-based mass spectrometers to transmit and detect a range of high molecular weight species is well documented. Herein, we describe how a 15 Tesla Fourier transform ion cyclotron resonance mass spectrometer (15 T FT-ICR MS) is more than capable of analyzing a wide range of ions in the high m/z scale (>5000), in both positive and negative instrument polarities, ranging from the inorganic cesium iodide salt clusters; a humanized IgG1k monoclonal antibody (mAb; 148.2 kDa); an IgG1-mertansine drug conjugate (148.5 kDa, drug-to-antibody ratio; DAR 2.26); an IgG1-siRNA conjugate (159.1 kDa; ribonucleic acid to antibody ratio; RAR 1); the membrane protein aquaporin-Z (97.2 kDa) liberated from a C8E4 detergent micelle; the empty MSP1D1-nanodisc (142.5 kDa) and the tetradecameric chaperone protein complex GroEL (806.2 kDa; GroEL dimer at 1.6 MDa). We also investigate different regions of the FT-ICR MS that impact ion transmission and desolvation. Finally, we demonstrate how the transmission of these species and resultant spectra are highly consistent with those previously generated on both quadrupole-ToF (Q-ToF) and Orbitrap instrumentation. This article serves as an impactful example of how FT-ICR mass analyzers are competitive to Q-ToFs and Orbitraps for high mass detection at high m/z.

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Research Organization:: Univ. of California, Los Angeles, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: FC02-02ER63421

OSTI ID:: 1799611

Journal Information:: Journal of the American Society for Mass Spectrometry, Vol. 31, Issue 5; ISSN 1044-0305

Publisher:: American Society for Mass SpectrometryCopyright Statement

Country of Publication:: United States

Language:: English

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
biochemistry & molecular biology
chemistry
spectroscopy
fourier transform ion cyclotron resonance
native-MS
monoclonal antibodies
cesium iodide
membrane proteins
antibody drug conjugates
siRNA
nanodiscs
GroEL

Title: High Mass Analysis with a Fourier Transform Ion Cyclotron Resonance Mass Spectrometer: From Inorganic Salt Clusters to Antibody Conjugates and Beyond

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