Multiple ion isolation applications in FT-ICR MS: exact-mass MSn internal calibration and purification/interrogation of protein-drug complexes.
Two new applications using multiple ion isolations in the cell of a Fourier transform-ion cyclotron resonance mass spectrometer equipped with an electrospray ionization source are described. A procedure that uses multiple ion isolations of an analyte and calibrants for internal calibration at each stage in a MSn experiment, under high-resolution exact-mass conditions, for structural characterization/elucidation of angiotensin I and rapamycin is illustrated. Fragment ion mass accuracies < 1.0 ppm are demonstrated and routinely achieved. Purification of a mixture is illustrated by isolating multiple charge states of a protein-drug complex from residual protein for further MSn studies to elucidate the site of covalent drug bonding using IRMPD for a mixture of epidermal growth factor receptor (EGFr) protein and EGFr-drug complex. The procedure developed for multiple ion isolations is referred to as multi-CHEF, multiple correlated harmonic excitation fields, in which tailored waveforms are used to notch out multiple mass regions of a spectrum with minimal off-resonance excitation.
Kruppa
Gary
G
Bruker Daltonics Inc, Billerica, Massachusetts 01821, USA.
Schnier
Paul D
PD
Tabei
Keiko
K
Van Orden
Steven
S
Siegel
Marshall M
MM
D000803:Angiotensin I / Q000032:analysis / Q000493:pharmacokinetics; D000818:Animals; D001665:Binding Sites; D001920:Bradykinin / Q000032:analysis / Q000378:metabolism; D002138:Calibration; D017357:Cyclotrons; D066246:ErbB Receptors / Q000032:analysis / Q000378:metabolism; D005583:Fourier Analysis; D006801:Humans; D007477:Ions; D013058:Mass Spectrometry; D008555:Melitten / Q000032:analysis / Q000378:metabolism; D008970:Molecular Weight; D004364:Pharmaceutical Preparations / Q000032:analysis*; D010599:Pharmacokinetics; D011506:Proteins / Q000032:analysis / Q000378:metabolism*; D020123:Sirolimus / Q000032:analysis / Q000493:pharmacokinetics
D007477:Ions; D004364:Pharmaceutical Preparations; D011506:Proteins; D008555:Melitten; D000803:Angiotensin I; D066246:ErbB Receptors; D001920:Bradykinin; D020123:Sirolimus