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Home Fault Detection Methods-for-quantitative-analysis-by-tandem-mass-spectrometry

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 Methods for quantitative analysis by tandem mass spectrometry

Details
Inventors: Kushnir, Mark M.; Rockwood, Alan L.; Nelson, Gordon J.;
Assignee: University of Utah (Salt Lake City, UT)
Primary Examiner: Raymond; Edward
Assistant Examiner:
Attorney, Agent or Firm: Trecartin; Richard F. Dorsey & Whitney LLP

The present invention provides methods for high throughput analysis of analytes in complex mixtures for unresolved chromatographic peaks including specific embodiment for summing intensities for each mass transition of interest over a selected chromatographic peak (50) to generate a signal corresponding to total intensity for each transition (55, 60). The intensities are deconvoluted into intensities of individual analytes (65, 70), based on branching ratios acquired from authentic standards, and a comparison to calibration curve is performed to obtain a quantitative concentration measurement of a particular analyte in a sample.

DETAILED DESCRIPTION Embodiments of the present invention provide methods for deconvoluting contributions of a plurality of analytes utilizing a tandem mass spectrometry, or MS.
sup.
n signal.
A tandem mass spectrometry signal including a plurality of peak intensities, generally at one or more mass transitions, is obtained wherein a plurality of analytes in a sample contribute to at least one of said peak intensities.
A model is provided relating one or more peak intensities to a contribution intensity for each of said analytes.
A contribution intensity for one or more analytes is then calculated using the model.
A calibration curve for at least one of the analytes is provided relating contribution intensity to concentration.
Based on the calibration curve, a concentration for at least one analyte is determined.
In some embodiments, the model used includes a system of linear equations.
In some embodiments, the mass spectrometry signal contains a number of peaks at least equal to the number of the target analytes of interest.
In other embodiments, there are a greater number of signal peaks than target analytes, and in other embodiments there are fewer signal peaks than target analytes, and at least one signal peak is monitored at a plurality of collision energies.
In some embodiments, the model includes representing the mass spectrometry signal as a weighted sum of reference signals, each reference signal corresponding to one of said analytes.
Embodiments of the present invention further include performing a quantitative calibration with authentic standards, internal standards, external standards, or a combination of standards may be utilized.
In embodiments of the present invention, the target analytes include isobars, and the quantitative concentration of one or more isobars in a sample can be determined.
In some embodiments, the target analytes include isomers.



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