The present inventive concepts relate to determining an isotope ratio using mass spectrometry. Mass spectra of ions are obtained by generating ions, guiding the ions through a device having a mass transfer function that varies with ion current, providing at least some of the ions to a mass analyser and obtaining a mass spectrum of the ions and determining the ion current of the ions provided to the mass analyser. An isotope ratio of the ions is determined for each mass spectrum. Using the determined isotope ratio and determined ion current for each mass spectrum, a calibration relationship is determined that characterises the variation of the determined isotope ratios and the measured ion currents across the mass spectra. Then, a measured isotope ratio obtained at a determined ion current is adjusted using the calibration relationship to adjust the measured isotope ratio to an adjusted isotope ratio corresponding to a selected ion current.

A method of operating an electrostatic trapping mass analyzer, comprises: (a) operating the electrostatic trapping mass analyzer at a maximum resolution so as to acquire a transient signal; (b) partitioning the transient signal into signal segments; (c) while a quality metric is either less than a pre-determined minimum threshold or greater than a pre-determined maximum threshold value, performing the steps of: (i) defining a test transient as being equal to either a first one of the segments or a previously defined transient with an appended signal segment; (ii) calculating a mathematical transform of the test transient and thereby generating a spectrum of component frequencies; and (iii) determining the quality metric from the spectrum of component frequencies; and (d) setting an instrumental resolution to be employed for subsequent mass spectral data acquisitions in accordance with a length of the most-recently-defined test transient.

A method of calibrating a TOF-MS mass spectrum, to account for temperature changes, is disclosed. Ions are introduced into a Fourier Transform Mass Spectrometer and their mass to charge ratios are determined. Ions, including calibrant ions, are also introduced into a time of flight mass spectrometer and the mass to charge ratios of the calibrant ions at least are also determined. Specific peaks representative of calibrant ions are selected and matched between the TOF MS and FTMS spectra. The relative position of matched peaks in each spectrum is then used to determine a temperature correction factor for the TOF MS data, based upon the relative independence of the FTMS spectrum with respect to temperature.

A method of operating an electrostatic trapping mass analyzer, comprises: (a) operating the electrostatic trapping mass analyzer at a maximum resolution so as to acquire a transient signal; (b) partitioning the transient signal into signal segments; (c) while a quality metric is either less than a pre-determined minimum threshold or greater than a pre-determined maximum threshold value, performing the steps of: (i) defining a test transient as being equal to either a first one of the segments or a previously defined transient with an appended signal segment; (ii) calculating a mathematical transform of the test transient and thereby generating a spectrum of component frequencies; and (iii) determining the quality metric from the spectrum of component frequencies; and (d) setting an instrumental resolution to be employed for subsequent mass spectral data acquisitions in accordance with a length of the most-recently-defined test transient.

A method of operating a Fourier Transform (FT) mass analyzer, which has a plurality of selectable resolving power settings, includes storing an optimized voltage value in association with each one of the plurality of selectable resolving power settings. More particularly, the optimized voltage values for at least two of the selectable resolving power settings differ from one another. When a user selects one of the plurality of selectable resolving power settings, the optimized voltage value that is stored in association therewith is retrieved. At least one voltage setting of the FT mass analyzer is controlled, based on the retrieved optimized voltage value, and an analytical scan is performed at the selected one of the plurality of selectable resolving power settings for a population of ions within the FT mass analyzer.

An electrostatic ion trap or an array of electrostatic ion traps are provided having a longitudinal length of no more than 10 mm and/or at least one electrode with a capacitance to ground of no more than 1 pF. First and second sets of planar electrodes may be distributed along the longitudinal axis, at least some of the which are configured to receive an electrostatic potential for confinement of ions received in the space between the first and second sets of planar electrodes. An array may comprise an inlet for receiving an ion beam, configured such that a portion of the ion beam can be trapped in each of the ion traps. Signals indicative of ion mass and charge data may be obtained from multiple electrostatic ion traps in the array. This mass and charge data may be combined for identification of components of a mixture of different analyte ions.

A method of operating a Fourier Transform (FT) mass analyzer, which has a plurality of selectable resolving power settings, includes storing an optimized voltage value in association with each one of the plurality of selectable resolving power settings. More particularly, the optimized voltage values for at least two of the selectable resolving power settings differ from one another. When a user selects one of the plurality of selectable resolving power settings, the optimized voltage value that is stored in association therewith is retrieved. At least one voltage setting of the FT mass analyzer is controlled, based on the retrieved optimized voltage value, and an analytical scan is performed at the selected one of the plurality of selectable resolving power settings for a population of ions within the FT mass analyzer.

Disclosed are methods for improving compound detection and characterization. Methods for characterizing a sample are disclosed. The methods can include providing a sample to a liquid chromatography system capable of sample separation to generate sample components; analyzing sample components by multiplexed targeted selected ion monitoring (SIM) to generate an inclusion list; and performing iterative mass spectral data-dependent acquisition (DDA) from the inclusion list, to identify individual sample components thereby characterizing the sample. In one example, multiplexed targeted SIMs and iterative MS2 DDA acquisition is used to increase robust compound identification for cell culture medium analysis.

A method and corresponding apparatus are disclosed for analysis of a peptide-containing sample. The sample is prepared by adding isotopically-labeled peptides corresponding to endogenous peptides of interest, and the prepared sample is analyzed by liquid chromatography-mass spectrometry (LCMS). Detection in a high-resolution, accurate mass (HRAM) MS1 spectrum of a precursor ion matching an isotopically-labeled peptide triggers acquisition of an MS/MS spectrum (preferably acquired in an ion trap or other fast mass analyzer) to determine if a product ion is present matching a characteristic product ion (e.g., the y.sub.1 ion) of the isotopically-labeled peptide. If the characteristic product ion is present, then a HRAM MS/MS spectrum is acquired for detection and quantitation of the corresponding endogenous peptide.

A mass spectrometer comprises: an ion source that generates ions having an initial range of mass-to-charge ratios; an auxiliary ion detector, downstream from the ion source that receives a plurality of first ion samples derived from the ions generated by the ion source and determines a respective ion current measurement for each of the plurality of first ion samples; a mass analyzer, downstream from the ion source that receives a second ion sample derived from the ions generated by the ion source and to generate mass spectral data by mass analysis of the second ion sample; and an output stage that establishes an abundance measurement associated with at least some of the ions generated by the ion source based on the ion current measurements determined by the auxiliary ion detector.