Identification and elimination of chemical noise for improved MS and MS / MS analysis

Abstract

Methods for mass spectrometry, which include the following: Mass analysis of ions and obtaining mass spectrum data, identification of precursor ions of interest, Determining a linear relationship between the mass / charge ratio of the precursor ions of interest and the mass / charge ratio of predicted noise peaks due to adductions, Determining the first noise peaks resulting from the adductions, which have mass / charge ratios corresponding to the linear relationship with the mass / charge ratio of the precursor ions of interest, and Removing the first noise peaks from the mass spectrum data.

Description

AREA OF INVENTION

[0001] The present invention relates generally to mass spectrometry and in particular to methods for mass spectrometry and mass spectrometers. BACKGROUND

[0002] In proteomics and other similar types of experiments, chemical noise or background ions (often of unknown origin) may be unintentionally counted or treated as analyte data, leading to lower scores or even false positive identifications when a library search is performed using MS and / or MS / MS data.

[0003] Part of the chemical "noise" consists of multiply charged clusters adducted to the analyte peptides. Multiply charged starting or precursor adductions, as well as fragment ions of such clusters, may also be present. The cluster adductions can originate from solvents.

[0004] US 2012 / 303288 A1 (Morinaga) discloses a data analysis method in which clustering is performed on standardized intensity value peaks, such that isotopic peak groups and adduction peaks derived from the same substance but with different mass / charge ratios are placed in the same clusters. Clusters deemed redundant are eliminated.

[0005] It is desirable to provide an improved method for mass spectrometry. SUMMARY

[0006] According to one aspect, a mass spectrometry procedure is provided which includes the following: Mass analysis of ions and obtaining mass spectrum data, Determining the starting or precursor ions of interest, Determining first adduct or chemical artifacts that have mass / charge ratios that are substantially linear with the mass / charge ratio of the starting or precursor ions of interest, and Eliminating or attenuating the first adduct or chemical artifacts from the mass spectrum data. According to one embodiment, a source ion (“MS”) or daughter ion (“MS / MS”) mass spectrum can be recorded or obtained, and a list of source or precursor ions can be identified. A list of ion peaks can then be calculated or otherwise determined from this list of source or precursor ions according to predefined relationships, for example, substantially linear relationships, between the source or precursor ions and predicted noise peaks, for example, due to adductions. The noise peaks (for example, adductions) can then be removed from the mass spectrum data to improve the specificity of the MS / MS data.

[0007] The embodiment relates to improved methods for removing chemical noise from mass spectrum data.

[0008] The embodiment differs from the arrangement disclosed in US 2012 / 303288 A1 (Morinaga) in that adduct or chemical artifacts are identified on the basis of an essentially linear relationship between the mass / charge ratios of the adduct or chemical artifacts and the mass / charge ratio of the starting or precursor ions of interest.

[0009] Furthermore, the mass / charge ratio transmission window of a mass filter can be progressively sampled using this method.

[0010] The mass filter can include a quadrupole bar-set mass filter.

[0011] The process can also be designed so that the mass filter passes on the starting or precursor ions of interest and attenuates or filters other starting or precursor ions.

[0012] Furthermore, the starting or precursor ions of interest can be subjected to fragmentation or reaction in the process to produce fragments or products.

[0013] The first adduct or chemical artifacts may exhibit a non-random distribution of the mass / charge ratio.

[0014] The first adduct or chemical artifacts may include: (i) singly charged adductions, (ii) doubly charged adductions, (iii) triply charged adductions, (iv) quadruply charged adductions, or (v) adductions with five or more charges.

[0015] The first adduct or chemical artifacts may include adductions that have lost or gained a neutral species or molecule.

[0016] The method may further include: determining second and / or further adduct or chemical artifacts having mass / charge ratios that have a substantially linear relationship with the mass / charge ratio of the starting or precursor ions of interest, and eliminating or attenuating the second and / or further adduct or chemical artifacts from the mass spectrum data.

[0017] The second and / or subsequent adduct or chemical artifacts may have a non-random distribution of the mass / charge ratio.

[0018] The second and / or subsequent adduct or chemical artifacts may include: (i) singly charged adductions, (ii) doubly charged adductions, (iii) triply charged adductions, (iv) quadruply charged adductions, or (v) adductions with five or more charges.

[0019] The second and / or subsequent adduct or chemical artifacts may include adductions that have lost or gained a neutral species or molecule.

[0020] According to another aspect, a mass spectrometer is provided which has a control system that is set up and designed to perform the following: (i) Mass analysis of ions and obtaining mass spectrum data, (ii) Determining the starting or precursor ions of interest, (iii) Determining first adduct or chemical artifacts having mass / charge ratios that are substantially linear with the mass / charge ratio of the starting or precursor ions of interest, and (iv) Eliminating or reducing the first adduct or chemical artifacts from the mass spectrum data.

[0021] The essentially linear relationship between the mass / charge ratios of the first adduct or chemical artifacts and the mass / charge ratio of the starting or precursor ions of interest may include a gradient relating to the charge of the starting or precursor ions and the charges of the first adduct or chemical artifacts.

[0022] The essentially linear relationship between the mass / charge ratios of the first adduct or chemical artifacts and the mass / charge ratio of the starting or precursor ions of interest may include an offset relating to the mass and charge of the starting or precursor ions.

[0023] According to another aspect, a mass spectrometry procedure is provided which includes the following: Mass analysis of ions and obtaining mass spectrum data, Determining the starting or precursor ions of interest, Determining first adduct or chemical artifacts that have mass / charge ratios that have a predetermined relationship with the mass / charge ratio of the starting or precursor ions of interest, and Eliminating or attenuating the first adduct or chemical artifacts from the mass spectrum data.

[0024] According to another aspect, a mass spectrometer is provided which has a control system that is set up and designed to perform the following: (i) Mass analysis of ions and obtaining mass spectrum data, (ii) Determining the starting or precursor ions of interest, (iii) Determining first adduct or chemical artifacts having mass / charge ratios that have a predetermined relationship with the mass / charge ratio of the starting or precursor ions of interest, and (iv) Eliminating or reducing the first adduct or chemical artifacts from the mass spectrum data.

[0025] According to one embodiment, the mass spectrometer may further include the following: (a) an ion source selected from the group consisting of: (i) an electrospray ionization (“ESI”) ion source, (ii) an atmospheric pressure photoionization (“APPI”) ion source, (iii) an atmospheric pressure chemical ionization (“APCI”) ion source, (iv) a matrix-assisted laser desorption ionization (“MALDI”) ion source, (v) a laser desorption ionization (“LDI”) ion source, (vi) an atmospheric pressure ionization (“API”) ion source, (vii) a desorption ionization on silicon (“DIOS”) ion source, (viii) an electron impact (“El”) ion source, (ix) a chemical ionization (“Cl”) ion source, (x) a field ionization (“Fl”) ion source, (xi) a (xii) field desorption (“FD”) ion source, (xii) an inductively coupled plasma (“ICP”) ion source, (xiii) a fast atom bombardment (“FAB”) ion source, (xiv) a liquid secondary ion mass spectrometry (“LSIMS”) ion source,(xv) a desorption electrospray ionization (“DESI”) ion source, (xvi) a radioactive nickel-63 ion source, (xvii) an atmospheric pressure matrix-assisted laser desorption ionization ion source, (xviii) a thermospray ion source, (xix) an atmospheric sampling glow discharge ionization (“ASGDI”) ion source, (xx) a glow discharge (“GD”) ion source, (xxi) an impactor ion source, (xxii) a direct analysis in real time (“DART”) ion source, (xxii) a laser spray ionization (“LSI”) ion source, (xxiv) a sonic spray ionization (“SSI”) ion source, (xxv) a matrix-assisted Intake ionization (“MAII”) ion source, (xxvi) a solvent-assisted intake ionization (“SAII”) ion source, (xxvii) a desorption electrospray ionization (“DESI”) ion source and (xxviii) a laser ablation electrospray ionization (“LAESI”) ion source and / or, (b) one or more continuous or pulsed ion sources and / or (c) one or more ion guides and / or (d) one or more ion mobility separation devices and / or one or more field asymmetric ion mobility spectrometer devices and / or (e) one or more ion traps or one or more ion containment areas and / or (f) one or more collision, fragmentation, or reaction cells selected from the group consisting of: (i) a collision-induced dissociation (“CID”) fragmentation device, (ii) a surface-induced dissociation (“SID”) fragmentation device, (iii) an electron transfer dissociation (“ETD”) fragmentation device, (iv) an electron capture dissociation (“ECD”) fragmentation device, (v) an electron impact or collision dissociation fragmentation device, (vi) a photo-induced dissociation (“PID”) fragmentation device, (vii) a laser-induced dissociation fragmentation device, (viii) an infrared radiation-induced dissociation device, (ix) an ultraviolet radiation-induced dissociation device, (x) a nozzle-skimmer interface fragmentation device, (xi) an in-source fragmentation device,(xii) an in-source impact-induced dissociation fragmentation device, (xiii) a thermal or temperature source fragmentation device, (xiv) an electric field-induced fragmentation device, (xv) a magnetic field-induced fragmentation device, (xvi) an enzyme digestion or enzyme degradation fragmentation device, (xvii) an ion-ion reaction fragmentation device, (xviii) an ion-molecule reaction fragmentation device, (xix) an ion-atom reaction fragmentation device, (xx) an ion-metastable ion reaction fragmentation device, (xxi) an ion-metastable molecule reaction fragmentation device, (xxii) a ion-metastable atom reaction fragmentation device, (xxiii) an ion-ion reaction device for reacting ions to form adducts or productions, (xxiv) an ion-molecule reaction device for reacting ions to form adducts or productions,(xxv) an ion-atom reaction device for reacting ions to form adducts or productions, (xxvi) an ion-metastable ion reaction device for reacting ions to form adducts or productions, (xxvii) an ion-metastable molecule reaction device for reacting ions to form adducts or productions, (xxviii) an ion-metastable atom reaction device for reacting ions to form adducts or productions, and (xxix) an electron ionization dissociation ("EID") fragmentation device and / or, (g) a mass analyzer selected from the group consisting of: (i) a quadrupole mass analyzer, (ii) a two-dimensional or linear quadrupole mass analyzer, (iii) a Paul or three-dimensional quadrupole mass analyzer, (iv) a Penning trap mass analyzer, (v) an ion trap mass analyzer, (vi) a magnetic sector mass analyzer, (vii) an ion cyclotron resonance (“ICR”) mass analyzer, (viii) a Fourier transform ion cyclotron resonance (“FTICR”) mass analyzer, (ix) an electrostatic mass analyzer configured to generate an electrostatic field with a quadrologarithmic potential distribution, (x) an electrostatic Fourier transform mass analyzer, (xi) a Fourier transform mass analyzer, (xii) a time-of-flight mass analyzer,(xiii) an orthogonal acceleration time-of-flight mass analyzer and (xiv) a linear acceleration time-of-flight mass analyzer and / or, (h) one or more energy analyzers or electrostatic energy analyzers and / or (i) one or more ion detectors and / or (j) one or more mass filters selected from the group consisting of: (i) a quadrupole mass filter, (ii) a two-dimensional or linear quadrupole ion trap, (iii) a Paul or three-dimensional quadrupole ion trap, (iv) a Penning ion trap, (v) an ion trap, (vi) a magnetic sector mass filter, (vii) a time-of-flight mass filter, and (viii) a Wien filter and / or (k) a device or ion gate for pulsing ions and / or (l) a device for converting a substantially continuous ion beam into a pulsed ion beam.

[0026] The mass spectrometer may also have one of the following features: (i) a C-trap and a mass analyzer comprising an outer tubular electrode and a coaxial inner spindle-shaped electrode forming an electrostatic field with a quadrologarithmic potential distribution, wherein in a first operating mode ions are transferred to the C-trap and then injected into the mass analyzer, and wherein in a second operating mode ions are transferred to the C-trap and then transferred to a collision cell or electron transfer dissociation device where at least some ions are fragmented into fragment ions, and wherein the fragment ions are then transferred to the C-trap before being injected into the mass analyzer, and / or (ii) a ring-stack ion guide with multiple electrodes, each having an opening through which ions are allowed to pass during use, wherein the distance between the electrodes increases along the ion path, and wherein the openings in the electrodes in an upstream section of the ion guide have a first diameter, and wherein the openings in the electrodes in a downstream section of the ion guide have a second diameter which is smaller than the first diameter, and wherein opposite phases of an alternating or RF voltage are applied to successive electrodes during use.

[0027] According to one embodiment, the mass spectrometer further comprises a device that is set up and designed to supply an alternating or RF voltage to the electrodes. The alternating or RF voltage preferably has an amplitude selected from the group consisting of the following: (i) approximately < 50 V peak-to-peak, (ii) approximately 50–100 V peak-to-peak, (iii) approximately 100–150 V peak-to-peak, (iv) approximately 150–200 V peak-to-peak, (v) approximately 200–250 V peak-to-peak, (vi) approximately 250–300 V peak-to-peak, (vii) approximately 300–350 V peak-to-peak, (viii) approximately 350–400 V peak-to-peak, (ix) approximately 400–450 V peak-to-peak, (x) approximately 450–500 V peak-to-peak and (xi) approximately > 500 V peak-to-peak.

[0028] The alternating or RF voltage can have a frequency selected from the following group: (i) < about 100 kHz, (ii) about 100–200 kHz, (iii) about 200–300 kHz, (iv) about 300–400 kHz, (v) about 400–500 kHz, (vi) about 0.5–1.0 MHz, (vii) about 1.0–1.5 MHz, (viii) about 1.5–2.0 MHz, (ix) about 2.0–2.5 MHz, (x) about 2.5–3.0 MHz, (xi) about 3.0–3.5 MHz, (xii) about 3.5–4.0 MHz, (xiii) about 4.0–4.5 MHz, (xiv) about 4.5–5.0 MHz, (xv) approximately 5.0 - 5.5 MHz, (xvi) approximately 5.5 - 6.0 MHz, (xvii) approximately 6.0 - 6.5 MHz, (xviii) approximately 6.5 - 7.0 MHz, (xix) approximately 7.0 - 7.5 MHz, (xx) approximately 7.5 - 8.0 MHz, (xxi) approximately 8.0 - 8.5 MHz, (xxii) approximately 8.5 - 9.0 MHz, (xxiii) approximately 9.0 - 9.5 MHz, (xxiv) approximately 9.5 - 10.0 MHz and (xxv) > approximately 10.0 MHz.

[0029] The mass spectrometer may also include a chromatography or other separation device upstream of an ion source. According to one embodiment, the chromatography separation device comprises a liquid chromatography or gas chromatography device. According to another embodiment, the separation device may comprise: (i) a capillary electrophoresis (“CE”) separation device, (ii) a capillary electrochromatography (“CEC”) separation device, (iii) a separation device with a substantially rigid ceramic-based multilayer microfluidic substrate (“ceramic tile”), or (iv) a supercritical fluid chromatography separation device.

[0030] The ion guidance can be maintained at a pressure selected from the group consisting of the following: (i) < about 0.0001 mbar, (ii) about 0.0001 - 0.001 mbar, (iii) about 0.001 - 0.01 mbar, (iv) about 0.01 - 0.1 mbar, (v) about 0.1 - 1 mbar, (vi) about 1 - 10 mbar, (vii) about 10 - 100 mbar, (viii) about 100 - 1000 mbar and (ix) > about 1000 mbar.

[0031] According to one embodiment, analyte ions can be subjected to electron transfer dissociation (“ETD”) fragmentation in an electron transfer dissociation fragmentation device. The analyte ions can be caused to interact with ETD reagents within an ion guide or fragmentation device.

[0032] According to one embodiment, to effect electron transfer dissociation, either: (a) analyte ions are fragmented or dissociated to form product or fragment ions after interacting with reagent ions, and / or (b) electrons are transferred from one or more reagent anions or negatively charged ions to one or more multiply charged analyte cations or positively charged ions, whereupon at least some of the multiply charged analyte cations or positively charged ions are dissociated to form product or fragment ions, and / or (c) analyte ions are fragmented or dissociated to form product or fragment ions after interacting with neutral reagent gas molecules or atoms or a non-ionic reagent gas.and / or (d) electrons are transferred from one or more neutral non-ionic or uncharged starting gases or vapors to one or more multiply charged analyte cations or positively charged ions, whereupon at least some of the multiply charged analyte cations or positively charged ions are caused to dissociate and form product or fragment ions, and / or (e) electrons are transferred from one or more neutral non-ionic or uncharged superbase reagent gases or vapors to one or more multiply charged analyte cations or positively charged ions, whereupon at least some of the multiply charged analyte cations or positively charged ions are caused to dissociate and form product or fragment ions, and / or (f) electrons are transferred from one or more neutral,(a) electrons are transferred from one or more non-ionic or uncharged alkali metal gases or vapors to one or more multiply charged analyte cations or positively charged ions, whereupon at least some of the multiply charged analyte cations or positively charged ions are caused to dissociate and form product or fragment ions, and / or (g) electrons are transferred from one or more neutral, non-ionic or uncharged gases, vapors or atoms to one or more multiply charged analyte cations or positively charged ions, whereupon at least some of the multiply charged analyte cations or positively charged ions are caused to dissociate and form product or fragment ions, wherein the one or more neutral, non-ionic or uncharged gases, vapors or atoms are selected from the group consisting of: (i) sodium vapor or atoms, (ii) lithium vapor or atoms, (iii) potassium vapor or atoms,(iv) rubidium vapor or atoms, (v) cesium vapor or atoms, (vi) francium vapor or atoms, (vii) C, 60 -vapor or atoms and (viii) magnesium vapor or atoms.

[0033] The multiply charged analyte cations or positively charged ions can include peptides, polypeptides, proteins, or biomolecules.

[0034] According to one embodiment, to effect electron transfer dissociation: (a) the reagent anions or negatively charged ions are derived from a polyaromatic hydrocarbon or a substituted polyaromatic hydrocarbon and / or (b) the reagent anions or negatively charged ions are derived from the group consisting of: (i) anthracene, (ii) 9,10-diphenylanthracene, (iii) naphthalene, (iv) fluorine, (v) phenanthrene, (vi) pyrene, (vii) fluoranthene, (viii) chrysene, (ix) triphenylene, (x) perylene, (xi) acridine, (xii) 2,2'-dipyridyl, (xiii) 2,2'-biquinoline, (xiv) 9-anthracenecarbonitrile, (xv) dibenzothiophene, (xvi) 1,10'-phenanthroline, (xvii) 9'-Anthracenecarbonitrile and (xviii) anthraquinone and / or (c) contain the reagents or negatively charged ions azobenzene anions or azobenzene radical anions.

[0035] According to one embodiment, the electron transfer dissociation fragmentation process involves analyte ions interacting with reagents, wherein the reagents include dicyanobenzene, 4-nitrotoluene or azulene. BRIEF DESCRIPTION OF THE DRAWING

[0036] Various embodiments are now described only as examples and with reference to the accompanying drawing. It shows: Fig. 1A an MS-MS / MS thermal map of the peptide bradykinin, wherein lines of chemical noise are represented which, according to one embodiment, have been identified as relating to adductions, wherein the adductions are subsequently removed from mass spectrum data to improve the specificity of MS / MS data, and Fig. 1B a list of the starting or precursor ions and the fragment ions for each of the in Fig. 1A shows lines of chemical noise. DETAILED DESCRIPTION

[0037] As discussed above, it is known that chemical noise or background ions can be unintentionally counted or treated as analyte data, leading to lower scores or even false positive identifications when a library search is performed using MS or MS / MS data.

[0038] It is known that part of the chemical “noise” adducted to the analyte peptides themselves includes multiply charged clusters.

[0039] One embodiment will now be described with reference to the Fig. 1A and Fig. 1B described.

[0040] Fig.Figure 1A shows an MS-MS / MS heat map relating to the peptide bradykinin. The x-axis corresponds to starting or precursor ions selected by a quadrupole mass filter, and the y-axis corresponds to the mass-to-charge ratio of corresponding fragment ions generated by fragmenting specific starting or precursor ions selected by the quadrupole mass filter. The resulting fragment ions were then analyzed by a time-of-flight mass analyzer. The quadrupole mass filter was configured to perform analyses in 1 Da steps (1 Da = 1 g / mol or 1.66 × 10⁻⁶). -27 to jump (kg).

[0041] The embodiment relates to the finding that in the Fig. In the mass spectrum data shown in 1A, various noise lines exist. Furthermore, the embodiment relates to the finding that, for example, the noise lines y3 and y4 pass through point B2+ and are due to doubly charged bradykinin peptide ions (B). 2+) with a mass / charge ratio of 531. Similarly, the noise line y1 or y2 passes through point B1+ and corresponds to singly charged bradykinin peptide ions (B 1+ ) with a mass / charge ratio of 1060.

[0042] An important aspect of the embodiment is the recognition that essentially linear noise lines are present, and the fact that the noise lines in the Fig. The heat map shown in Figure 1A is shown to pass either through B1+ or through B2+. According to the embodiment, it is recognized that significant sources of chemical noise on the mass / charge ratio scale are not simply randomly distributed, but are intrinsically related to the sample or the starting or precursor ions of interest.

[0043] Apart from the parent or precursor ion diagonal line y = x and the MS / MS data (i.e., fragment ions derived from parent or precursor ions with a mass / charge ratio of, for example, 531, arranged along a vertical line, as in Fig. (as shown in 1B), there are several other significant lines which have been empirically designated as follows.

[0044] A noise line “y1” represents singly charged adductions after the loss of singly charged bradykinins. First, a doubly charged cluster species was selected by the quadrupole mass filter, consisting of an arbitrary variable adduct A. 1+ and bradykinin B 1+ This cluster (likely not covalently bound) loses bradykinin and its 1+ charge, leaving behind singly charged adductions A. These types of adductions lie along the noise line y1 = 2x - B.

[0045] A noise line “y2” represents the doubly charged adductions after the loss of singly charged bradykinins. Initially, a triply charged cluster species was selected by the quadrupole mass filter, consisting of adduct A. 2+ and bradykinin B 1+ This cluster loses bradykinin and its 1+ charge, leaving behind the doubly charged adductions A. These types of adductions lie along the noise line y2 = 1.5x - B / 2.

[0046] The noise line “y3” represents the doubly charged adductions after the loss of doubly charged bradykinins. Initially, a quadruply charged cluster species was selected by the quadrupole mass filter, consisting of adduct A. 2+ and bradykinin B 2+ This cluster loses bradykinin and its 2+ charge, leaving behind the doubly charged adductions A. These types of adductions lie along the noise line y3 = 2x - B / 2.

[0047] The noise line “y4” represents the singly charged adductions after the loss of doubly charged bradykinins. Initially, a triply charged cluster species was selected by the quadrupole mass filter, derived from adduct A. 1+ and bradykinin B 2+ This cluster loses bradykinin and its 2+ charge, leaving behind singly charged adductions A. These types of adductions lie along the noise line y4 = 3x - B.

[0048] Neutral loss / gain ions are also observed at the lines y = B and y = B / 2.

[0049] Other noise lines can also be identified and similarly filtered out from the final mass spectrum data.

[0050] The embodiment can therefore exploit noise patterns in the data identified according to the embodiment to enable the removal of ions from mass spectrum data that would otherwise interfere with MS / MS library searches.

[0051] To further explain the embodiment, a data-dependent detection (“DDA”) experiment may be considered in which several known starting or precursor ions elute essentially simultaneously and are identified in an overview scan as starting or precursor ions (corresponding to the molecular weights of) m1, m2, m3, m4 and m5.

[0052] If the parent or precursor ion m3 is identified as being of interest, the quadrupole can be set to m3 to only allow parent or precursor ions with a mass-to-charge ratio of m3 (or a value corresponding to the molecular weight of m3 based on its charge state) to pass through. These parent or precursor ions with a mass-to-charge ratio of m3 are then subjected to fragmentation to obtain MS / MS mass spectrum data.

[0053] According to the embodiment, to improve the MS / MS data, chemical artifacts associated with the starting or precursor ions m1, m2, m4, m5, which are not of interest, can be calculated using the equations in the table below (within a suitable window): Precursor m / z:m3 Noise m / z values ​​of m1 Noise m / z values ​​of m2 Noise m / z values ​​of m4 Noise m / z values ​​m5 Noise line y1 2*m3 - m1 2*m3 - m2 2*m3 - m4 2*m3 - m5 Noise line y2 1.5*m3 - m1 / 2 1.5*m3 - m2 / 2 1.5*m3 - m4 / 2 1.5*m3 - m5 / 2 Noise line y3 2*m3 - m1 / 2 2*m3 - m2 / 2 2*m3 - m4 / 2 2*m3 - m5 / 2 Noise line y4 3*m3 - m1 3*m3 - m2 3*m3 - m4 3*m3 - m5 Neutral loss / gain m1 / 2 m2 / 2 m4 / 2 m5 / 2 Neutral loss / gain m1 m2 m4 m5

[0054] It can be seen from the table that the noise lines show an essentially linear relationship with the mass / charge ratio (or a value corresponding to the molecular weight) of the starting or precursor ions m1, m2, m3, m4 and m5.

[0055] In the example, the values ​​of the noise line gradient include 0, 1, 1.5, 2, 3. It can be seen that the noise line gradient depends on the charges of the initial or precursor ions, the charges of the adduct, and the charges lost when the initial or precursor ions are lost.

[0056] In the example, the offset of the noise lines is determined by the molecular weight of the starting and precursor ions and their charges, where the offset of the noise lines for the noise of m1, for example, is a value derived from m1.

[0057] The chemical artifacts can be removed from the mass spectrum data once they have been calculated or otherwise determined, as detailed above.

Claims

[1] Methods of mass spectrometry which include: Mass analysis of ions and obtaining mass spectrum data, identification of precursor ions of interest, Determining a linear relationship between the mass / charge ratio of the precursor ions of interest and the mass / charge ratio of predicted noise peaks due to adductions, Determining the first noise peaks resulting from the adductions, which have mass / charge ratios corresponding to the linear relationship with the mass / charge ratio of the precursor ions of interest, and Removing the first noise peaks from the mass spectrum data. [2] Method according to claim 1, wherein a mass / charge ratio transmission window of a mass filter is progressively sampled. [3] Method according to claim 2, wherein the mass filter comprises a quadrupole rod mass filter. [4] Method according to claim 2 or 3, wherein the mass filter is further caused to preferably pass on the precursor ions of interest and to attenuate or filter other ions. [5] Method according to claim 4, wherein the precursor ions of interest are further subjected to fragmentation or reaction to produce products. [6] Method according to any of the preceding claims, wherein the adductions comprise: (i) singly charged adductions, (ii) doubly charged adductions, (iii) triply charged adductions, (iv) quadruply charged adductions or (v) adductions with five or more charges. [7] Method according to any of the preceding claims, wherein the adductions comprise adductions which have lost or gained a neutral species or a neutral molecule. [8] A method according to any of the preceding claims, further comprising: Determining further noise peaks resulting from further adductions that have mass / charge ratios that are linearly related to the mass / charge ratio of the precursor ions of interest, and Removing further noise peaks from the mass spectrum data. [9] Method according to claim 8, wherein the further adductions comprise: (i) singly charged adductions, (ii) doubly charged adductions, (iii) triply charged adductions, (iv) quadruply charged adductions or (v) adductions with five or more charges. [10] Method according to claim 8 or 9, wherein the further adductions comprise adductions which have lost or gained a neutral species or a neutral molecule. [11] Method according to any of the preceding claims, wherein the linear relationship comprises a gradient relating to the charge of the precursor ions and the charges of the adductions. [12] Method according to any of the preceding claims, wherein the linear relationship includes an offset relating to the mass and charge of the precursor ions. [13] Mass spectrometers with a control system that is set up and designed to perform the following: (i) Mass analysis of ions and obtaining mass spectrum data, (ii) Identifying precursor ions of interest, (iii) Determining a linear relationship between the mass / charge ratio of the precursor ions of interest and the mass / charge ratio of predicted noise peaks due to adductions, (iv) Determining first noise peaks resulting from adductions that have mass / charge ratios corresponding to the linear relationship with the mass / charge ratio of the precursor ions of interest, and (iv) Eliminating the first noise peaks from the mass spectrum data.

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