FR2914779A1 - Tandem mass spectrometry method involves determining real multiplets of charged fragments corresponding to parent primary ions by identifying multiplets meeting proximity criterion of correlation laws from potential multiplets - Google Patents

Abstract

The correlation laws that all multiplets of characteristics function values have to meet corresponding multiplets of charged fragments, are determined from characteristics function values at maxima of primary mass peaks and from the charge values associated to peaks. The real multiplets of charged fragments corresponding to the parent primary ions are determined by identifying the multiplets meeting a proximity criterion in relation to correlation laws from the potential multiplets. A dissociation mass spectra is generated corresponding to the parent primary ions. Independent claims are included for the following: (1) tandem mass spectrometer; and (2) tandem mass spectrometry program.

Description

Field of the invention

  The invention relates to a tandem mass spectrometry method without primary mass selection.

State of the art

  As a reminder, mass spectrometry (MS), of whatever type, generally comprises the steps of identifying molecules present in a sample by measuring the mass of these molecules after having been ionized, accelerated and introduced into a spectrometer. massive. The mass spectrometer produces a mass spectrum of the different molecules contained in the analyzed sample according to the value of the mass-to-charge ratio (M / Q) (M being the mass and Q the charge) of the ions produced in the form of the intensity of the ion current detected by an ion detector as a function of the variation of a function F (M / Q) of the mass-to-charge ratio of ions which depends on the mass spectrum used, which is generally of the form: F (M / Q) = G x (M / Q), where G is a function which depends on the type of spectrometer used independent of the mass-to-charge ratio of the ions.

  The main types of mass spectrometers used are time-of-flight mass spectrometers, magnetic sector spectrometers (B), quadrupole mass spectrometers (Q), ion traps (IT) 3D (hyperbolic geometry) or 2D linear (cylindrical geometry), and Fourier transform mass spectrometer FTICR acronym for Fourier Transform Ion Cyclotron Resonance. The specific operating modes of each type of mass spectrometer mentioned above, and their different variants are known to those skilled in the art. In the case of time-of-flight mass spectrometers, there is: F (M / Q) = TOF2 (M / Q) = GTOF x (M / Q), where TOF is the flight time of the ions. For example, for a linear flight time, we have: GTOF = (L 2/2 Vo), where L is the linear flight time distance between the ion packet pulsation and the ion detector, and Vo is the acceleration voltage of the ions. In the case of magnetic sector mass spectrometers one has: F (M / Q) = B2 (M / Q) = GB x (M / Q), where B is the variable magnetic field applied in the magnetic sector allowing to filter ions as a function of their charge mass ratio to an ion detect. For example, for a single focus magnetic sector, we have: GB = (2 Vo / R2) (M / Q> where R is the radius of the magnetic sector and Vo is the acceleration voltage of the ions. quadrupole mass one has: 15 F (M / Q) = VQ (M / Q) = GQ x (M / Q), where VQ is the variable voltage applied in the quadrupole to filter the ions according to their mass-to-charge ratio In the case of mass spectrometers of the ion trap type one has: F (M / Q) = VIT (M / Q) = GIT x (M / Q), where VIT is the voltage variable applied in the ion trap to eject the ions according to their mass-to-charge ratio to an ion detector In the case of Fourier Transform Ion Cyclotron Resonance Fourier transform mass spectrometers FTICR a: F ( M / Q) = {I / 0) FTICR (M / Q) = GFTICR x (M / Q), where cOFTICR is the cyclotron frequency corresponding to each ion mass-to-charge ratio (M / Q) of the ions whose measurement and analysis by Fourier transform makes it possible to produce the mass spectrum of the ions.

  There is also tandem mass spectrometry (MS-MS), generally used when the primary mass spectrum (MS) does not identify the molecules studied. It generally comprises the steps of producing, using a first mass spectrometer, a primary mass spectrum (MS) of the ionized molecules present in the sample analyzed, to perform a step of selecting a primary mass. , then to fragment, or otherwise dissociate, with a dissociation system the primary ions of said selected primary mass, so as to produce a so-called dissociation mass spectrum of the charged fragments from the dissociation of these primary ions using a second mass spectrometer. Primary mass selection to achieve each dissociation mass spectrum limits the acquisition rate of the tandem mass spectrometer used, since each mass spectrum is produced successively. It also limits the sensitivity of the tandem mass spectrometer used, defined as the amount of sample consumed to produce each dissociation mass spectrum, since the other unselected primary ions provided by the ion source are removed to produce the dissociation spectrum of the selected primary ions. The dissociation of the primary ions can be carried out at high kinetic energy (0.2-20 keV) or at low kinetic energy (ù10 eV). For example, the dissociation can be achieved by low kinetic energy (CID) (acronym for "Collision Induced Dissociation") with, for example, multiple collisions induced with the molecules of a gas in a waveguide, or by CID (acronym for "Collision Induced Dissociation") with high kinetic energy with one or two induced collisions with the molecules of a gas in a collision box. In the case of low kinetic energy dissociation the measurement of the mass-to-charge ratio (m / q) of the dissociated charged fragments is generally obtained in the same manner as that of the parent primary ions in the form of the current intensity. ions detected by an ion detector as a function of the variation of a function F (m / q) of the mass-to-charge ratio (m / q) which depends on the mass spectrum used which is also of the form: F ( m / q) = G x (m / q), where G is a function which depends on the type of spectrometer used independent of the mass-to-charge ratio of the ions.

  The F function of the mass spectrometer used does not depend on the kinetic energy of the undissociated primary ions and the charged fragments, because either the undissociated primary ions and the charged fragments are accelerated to the same kinetic energy before the mass spectrometer. the G-function of the mass spectrometer used to produce the dissociation spectra does not depend on the kinetic energy of the ions. In the case of high kinetic energy dissociation, the F '(m / q) function of the mass spectrometer used depends on the kinetic energy of the dissociated charged fragments, since the kinetic energy of the dissociated charged fragments depends on the mass of the fragments. . For the same mass spectrometer used, the function F (M / Q) for the measurement of the mass-to-charge ratio of the undissociated primary ions is therefore different from the function F '(m / q) for the measurement of the mass-to-charge ratio. dissociated charged fragments. The function F '(m / q) can not generally be in the form: F' (m / q) = G 'x (m / q), where G' would be a function that would depend on the independent mass spectrum used the mass-to-charge ratio of the dissociated charged fragments.

  In the particular case of time-of-flight mass spectrometry, in addition to the tandem flight time mass spectrometers previously described with primary mass selection, tandem flight time mass spectrometers are also known without selection of primary mass. They make it possible to produce several dissociation mass spectra simultaneously.

  Time-of-flight mass spectrometry methods are thus known without primary mass selection [1] [2] [3] [4], which nevertheless require several acquisitions to produce the different dissociation spectra, but with a number of successive acquisitions less compared to devices using primary mass selection.

  In particular, three tandem flight time mass spectrometry methods are known to produce several dissociation mass spectra without primary mass selection in a single acquisition [5] [6] [7]. The first of these is a time-of-flight mass spectrometry method without primary mass selection based on the transformation of flight times into measured positions [5]. This method limits the primary mass range accessible simultaneously. The second is a time-of-flight mass spectrometry method with no mass selection limited to mono-charged primary ions, based on the individual identification of each pair of dissociated fragments in neutral and charged fragment pairs [6], with no limit of the primary mass range accessible simultaneously. The third is a time-of-flight mass spectrometry method without mass selection limited to multicharged primary ions, based on the individual identification of pairs of fragments dissociated into charged fragment pairs [7], with no limit of the mass range. primary accessible simultaneously. Processes [1], [2], [3], [4], [5], and [6] are only compatible with dissociation of primary ions with high kinetic energy. Only the method [7] is compatible with both the dissociation of primary ions at low and high kinetic energy. But the method [7] requires an individual detection of charged fragments, and is therefore not compatible with tandem flight time mass spectrometers producing several ions per time channel at each pulse of the ion packet, such as by For example, the mass spectrometer combining an ion trap to produce each ion packet and a time-of-flight mass spectrometer (IT-TOF).

  The dissociation of the multicharged primary ions can be complex and give rise to several possible dissociation channels [8]. The three main dissociation channels are [8], if M and Q respectively are the mass and the electric charge of the parent primary ion and mi and qi are the mass and charge of each dissociated fragment i (with i = 1, 2 or 3): (a) M (Q) -> mi (gi) + m2 (g2), with mi + m2 = M and qi + qz = Q, (b) M (Q) where > mi (gi = Q + e) + m2 (q2 = 0), with mi + m2 = M, and e is the unit of electric charge, (c) M (Q) - * mi (qi) + m2 ( g2) + m3 (g3), with mi + m2 + m3 = M and qi + q2 + q3 = Q. Thus, even for dissociation mass spectra made with primary mass selection, the determination of the mass-to-charge ratio of Dissociation mass peaks obtained with multicharged parent primary ions, and therefore their identification, are difficult because of these different possible dissociation channels. The only tandem mass spectrometry method capable of selecting a single dissociation channel from the set of possible dissociation channels of the multicharged primary ions is the method [7] which produces the dissociation spectra only for the dissociating primary ions in pairs of charged fragments.

  Fragments of charged fragments with mono-charged primary ions can also be produced by ionizing the neutral fragments from the dissociation of the mono-charged primary ions into pairs of neutral and charged fragments. This ionization of the dissociated neutral fragments can be carried out, for example, in the ion source which simultaneously ionizes and dissociates the ions, following the technique of dissociation in the source of ISD ions, acronym for In Source Decay. Electron impact ion sources are an example of this type of mono-charged ion sources.

  There is currently no universal tandem mass spectrometry method for producing multiple dissociation spectra simultaneously without primary mass selection for multicharged and / or mono-charged primary ions compatible with all existing mass spectrometry techniques.

  SUMMARY OF THE INVENTION The object of the invention is therefore to overcome the disadvantages of the state of the art presented in particular above, in the case of multicharged and / or mono-charged primary ions. In particular, an object of the invention is in particular to propose a method of mass spectrometry without primary mass selection capable of producing simultaneously in a single acquisition all of all the dissociation spectra of all the different primary masses present in a sample to be analyzed for primary ions dissociating only in pairs of charged fragments. For this purpose, a tandem flight time mass spectrometry method comprising the following steps is proposed according to the invention: a source of primary ions to be analyzed is provided; a primary mass spectrum of the ions is generated; This spectrum contains peaks of occurrences of primary ions, from this spectrum, it is determined for each of the primary mass peaks that it contains the value of the function dependent on the mass-to-charge ratio of the ions. The primary ions of the mass spectrometer used, corresponding to the maximum number of occurrences of this peak, and the electric charge of the primary ions, 20 - from these data, correlation laws are determined in the form of linear equations of each of the primary mass peaks, giving all possible pairs of values of the mass-to-charge ratio function of dissociated charged fragments of the mass spectrometer used, corresponding to peaks of occurrence of possible pairs of dissociation mass peaks produced by 25 pairs of charged mass-to-charge ratio fragments likely to result from the dissociation of identical primary ions having the same mass-to-charge ratio, - primary ions are dissociated without selection of primary mass, at low kinetic energy, so as to obtain for each of them, a pair of charged fragments, - one generates a dissociation spectrum without primary mass selection containing the dissociation mass peaks of each of the spectra of dissociation corresponding to each primary mass peak, - from this spectrum, for each of the dissociation mass peaks that it contains, each value of the function of the mass-to-charge ratio of the dissociated charged fragments of the corresponding mass spectrometer used is determined. at most occurrences of this peak, - one generates from the measured values of the function of the report mass on load of the fr dissociated charged agings of the mass spectrometer used corresponding to the maxima of occurrences of the dissociation peaks all the potential pairs of these values, - from among said potential pairs, the actual pairs which satisfy a criterion of proximity with respect to the correlation laws are identified; , and thus identify the pairs of dissociation mass peaks corresponding to the same peak of the primary mass spectrum, each dissociation spectrum corresponding to each of the primary mass peaks is produced, with the pairs of dissociation mass peaks corresponding to the 15 real pairs identified.

  Preferred but non-limiting aspects of this method are the following: * The dissociated charged fragment pairs arise from the low kinetic energy dissociation of multicharged primary ions, and are also derived from low energy dissociation. kinetics of multicharged primary ions in pairs of neutral and charged fragments, then ionization of the neutral fragments.

  * The pairs of dissociated mono-charged fragments are first derived from the dissociation at low kinetic energy of mono-charged primary ions in pairs of neutral and mono charged fragments, then the ionization of the neutral fragments.

  the step of identification of the real pairs comprises the following sub-steps: a two-dimensional mass spectrum having two first dimensions each representing the measured values of the function of the mass-to-charge ratio of the dissociated charged fragments of the spectrometer of mass used corresponding to the maximum of occurrences of each of the dissociation peaks, the position of each occurrence of detection in the plane defined by the two dimensions corresponding to a potential pair of these values, - it is positioned in this same plane of the characteristic lines determined by the linear equations of these correlation laws, we position in the same plane the occurrences corresponding to each potential pair of values, and we identify, among the potential pairs of values, those having a position of occurrence, in said plane which lies at a distance from one of the characteristic lines less than a This is to identify the actual pairs of values corresponding to actual pairs of dissociation mass peaks produced by pairs of charged fragments from the dissociation of identical primary ions with the same mass-to-charge ratio.

  Another object of the invention is to propose a tandem mass spectrometer comprising, according to the general direction of movement of the ions: an ion source (1); means for supplying a primary mass spectrum of these ions; primary ions from these ionized molecules, so as to be able to identify the value of the mass-to-charge ratio function of the primary ions of the mass spectrometer used corresponding to the maximum number of occurrences and the primary electric charge, corresponding to each mass peak primary of these ions, - a device for dissociating (2) the primary ions so as to obtain, for each of them, a pair of charged fragments, - a mass spectrometer (3), producing the primary mass spectrum of the ions 25, and the dissociation spectrum without primary mass selection of charged fragments, an ion detector (4), identification means, in the set of dissociation mass peaks, peak pairs s of dissociation mass corresponding to pairs of charged fragments resulting from the dissociation of primary ion parents with the same mass to charge ratio, these identification means being arranged so that the identification is based on the measured values of the function of the mass-to-charge ratio of the dissociated charged fragments of the mass spectrometer used corresponding to the maxima of occurrences of the dissociation mass peaks, and of predetermined correlation laws, giving the possible pairs of these values.

  Another object of the invention is to propose a tandem mass spectrometer comprising, according to the direction of general displacement of the ions: an ion source (1), means for supplying a primary mass spectrum of these ions primary to from these ionized molecules, so as to be able to identify the value of the mass-to-charge ratio function of the primary ions of the mass spectrometer used corresponding to the maximum number of occurrences and the primary electric charge, corresponding to each primary mass peak of these ions, - an ion trap (5) for storing the ions emitted by the ion source (1) before their injection into the device for dissociating the primary ions in pairs of charged fragments (2), - means to inject in the device of dissociation of the primary ions in pairs of charged fragments (2), only the primary ions coming from the primary mass peaks of the molecules to be identified, - a dissociation device of primary ions in pairs of charged fragments (2), -a mass spectrometer (3), producing the primary mass spectrum of the primary ions, and the dissociation spectrum without primary mass selection of charged fragments, -a detector of Ions (4), means for identifying, in the set of dissociation mass peaks, pairs of dissociation mass peaks corresponding to pairs of charged fragments resulting from the dissociation of primary primary ions and the like. mass-to-charge ratio, said identification means being arranged so that the identification is based on the measured values of the mass-to-charge ratio function of the dissociated charged fragments of the mass spectrometer used corresponding to the maxima of occurrences of the peaks of mass dissociation, and predetermined laws, called correlation, giving the possible pairs of these values.

  Preferred, but not limiting, aspects of these tandem mass spectrometers are as follows: the source of primary ions (1) is a source of multicharged and / or mono-charged ions, the dissociation device ( 2) Primary ions in pairs of charged fragments is equipped with a system ionizing the neutral fragments from the dissociation at low kinetic energy of the primary ions.

  Preferred, but not limiting, aspects of these tandem mass spectrometers are as follows: the dissociation device (2) producing the dissociated charged fragment pairs is an ion trap containing low kinetic energy dissociating gas the primary ions by multiple collisions with the gas molecules, - the ion trap (2) is equipped with a system ionizing the neutral fragments resulting from the dissociation at low kinetic energy of the primary ions in the ion trap (2), The ion trap forming the dissociation device (2), for primary ions, or dissociated charged fragments, of the same mass-to-charge ratio previously selected with the mass selection mode of the ion trap, produces pairs of charged fragments, by performing two successive steps of dissociations by collision with the gas molecules and neutral fragment ionizations, without primal mass selection. areas of the dissociated charged fragments produced at each of the two stages.

  Preferred but non-limiting aspects of these tandem mass spectrometers are as follows: the device for dissociation (2) of the primary ions in pairs of charged fragments at low kinetic energy is a multipole waveguide containing gas dissociating the primary ions by multiple collisions with the gas molecules, - the multipole waveguide is equipped with a system ionizing the neutral fragments from the low kinetic energy dissociation of the primary ions in the multipole waveguide (2) .

  Another object of the invention is to propose a computer program that can be implemented in a time-of-flight-to-tandem time-of-flight mass spectrometry system and comprises a set of instructions able to perform the following steps: command the system to generate from a source of primary ions to be analyzed, a primary mass spectrum of these primary ions, without dissociation, this spectrum containing peaks of occurrences of primary ions, - is carried out an acquisition of the data of this spectrum, 15 - from said data, for each of the primary mass peaks it contains, the value of the mass-on-charge function of the primary ions of the mass spectrometer used, corresponding to the maximum of occurrences of this peak, and the electric charge of the primary ions, - from these peak data, correlation laws are determined giving all possible pairs of values of the function of the ratio ma on charge of dissociated charged fragments of the mass spectrometer used corresponding to maxima of occurrences of possible pairs of dissociation mass peaks produced by pairs of charged fragments from the different primary ions, - the system is controlled so that causes the dissociation of the primary ions at low kinetic energy so as to obtain for each of them, a pair of charged fragment, - is generated, without selection of primary mass, a dissociation spectrum of these dissociated charged fragments containing the peaks of dissociation mass of each of the dissociation spectra corresponding to each primary mass peak, from this spectrum, for each of the dissociation mass peaks which it contains, each value of the function of the mass-to-charge ratio of the dissociated charged fragments of the mass spectrometer used corresponding to the maximum of occurrences of this peak, - one generates from s measured values all the potential pairs of these values, - from among said potential pairs, the real pairs which satisfy a criterion of proximity with respect to the correlation laws are identified, and thus the pairs of dissociation mass peaks corresponding to the At the same peak of the primary mass spectrum, each dissociation spectrum corresponding to each of the primary mass peaks is produced, with the pairs of dissociation mass peaks corresponding to the actual identified pairs. BRIEF DESCRIPTION OF THE FIGURES Other aspects, objects and advantages of the invention will appear better on reading the following description of the invention, given by way of non-limiting example, and with reference to the appended drawings in which: FIG. 1 is a flowchart of a preferred embodiment of the spectrometry method according to the invention; FIG. 2 illustrates components of a system capable of implementing the mass spectrometry method according to an example of FIG. FIG. 3 illustrates a primary mass spectrum of molecules to be identified, having three primary mass peaks; FIG. 4 illustrates a dissociation mass spectrum obtained without primary mass selection, including mass peaks; of the three dissociation spectra of the three primary mass peaks of the primary mass spectrum example of FIG. 3, with some of the measured values Finax (m / q) of the mass ratio function on charge of the dissociated charged fragments of the mass spectrometer used, corresponding to the maximum of occurrence of each dissociation mass peak; FIG. 5 illustrates the three dissociation spectra of the three primary mass peaks of FIG. according to the invention, from the dissociation spectrum without primary mass selection of FIG. 4, FIG. 6 illustrates in the plane {Finax (mr / gr '), Finax (ms / gs')} of the spectrum two-dimensional, three examples of straight lines characteristic of multicharged primary ions dissociating into pairs of charged fragments, corresponding to the correlation laws of three primary mass peaks, each primary mass peak corresponding to a different primary charge (Q '1 = 2 e , Q'2 = 3 e and Q'3 = 4 e, where e is the electric charge unit), - Figure 7 illustrates the plane {Finax (mr / gr '), Finax (ms / qs')} of a two-dimensional spectrum comprising only three characteristic lines corresponding to in three double-charged primary ion mass peaks of Figure 3, dissociating without primary mass selection into charged fragment pairs. The positions in the {Finax (m / g)}, Fmax (ms / gs')} plane of the two-dimensional spectrum of potential and actual pairs of values of the mass-to-charge ratio function of the dissociated charged fragments of the corresponding mass spectrometer used at the peaks of occurrences of the dissociation peaks of FIG. 4 are also shown in the figure; FIG. 8 illustrates a tandem mass spectrometer according to one embodiment of the invention, with an ion trap positioned between the ion source and the dissociation device producing the charged fragment pairs.

  Description of Embodiments of the Invention

  It is recalled as a preliminary that the term multi-charged ion means an ion 25 having a positive or negative electric charge of absolute value greater than or equal to 2 e (where e is the unit of electric charge). Referring in particular to FIG. 1, the method according to the invention aims to dissociate the multicharged primary ions into pairs of charged fragments, and to dissociate the multicharged primary ions into neutral fragment pairs and charged with ionization of the dissociated neutral fragments, eliminating the other possible channels of dissociation.

  With reference also to FIG. 1, the method according to the invention aims at the dissociation of the mono-charged primary ions into pairs of mono-charged fragments, the second charged mono-fragment originating from the ionization of a neutral fragment originating from the dissociation of the ions. mono-charged primers in neutral and mono-charged fragment pairs, removing the dissociation channel in pairs of neutral and mono-charged fragments without ionization of the neutral moiety.

  In the present embodiment, we first provide a primary mass spectrum of primary ions from molecules that are to be identified without dissociation. This primary mass spectrum can be obtained by reading from a database, such as a third-party database, in which it has previously been saved. It can also be obtained by carrying out steps (a) and (b) illustrated in FIG. 1. In step (a) of this figure, the molecules to be identified are ionized in an ion source, represented in Figure 2 by the reference (1), and accelerates with a generally constant electric field. Then in step (b), the primary ions are injected into the mass spectrometer used (3), and then measured as a function of the variation of the function F (M / Q) of the mass spectrometer used (3). , the occurrences (or the intensity of the ion current) of the primary ions detected by the ion detector (4). The function F (M / Q) is of the form: F (M / Q) = G x (M / Q), where G is a function which depends on the mass spectrometer used (3) independent of the mass-to-charge ratio ions, and M / Q is the mass-to-charge ratio of the primary ions. The primary mass spectrum (MS) is then produced based on these measurements.

  According to the usual graphical presentation in mass spectrometry, conventionally used by those skilled in the art (but not limited to), the primary mass spectrum is generally represented with two perpendicular axes, with the measured values of the function F on the abscissa (M / Q), and ordinate the occurrences (or intensity of the detected ion current) corresponding.

  This primary mass spectrum then makes it possible to determine, in a step (c), the value Finax (M / Q) of the mass-to-charge ratio function of the primary ions of the mass spectrometer used corresponding to the maximum number of occurrences and the load primary electric Q primary ions, corresponding to each primary mass peak. Those skilled in the art can determine the charge Q for multicharged primary ions corresponding to each primary mass peak with the identification techniques usually used in mass spectrometry.

  In addition, it will be able to determine the values of each primary charge mass ratio (M / Q) of the primary ions corresponding to each primary mass peak, by performing the usual preliminary primary calibration of the mass spectrometer used, with known molecules. FIG. 3 shows an example of a primary mass spectrum containing three primary mass peaks of primary ions, respectively of mass-to-charge ratio, (M1 / Q1), (M2 / Q2), and (M3 / Q3), with the Fmax (M / Q) values of the mass-to-charge ratio function of the primary ions of the mass spectrometer used corresponding to the maximum number of occurrences of each of these primary mass peaks.

  In a step (d), determined from these data, laws, called correlation, of each of the primary mass peaks, giving all possible pairs {Finax (mk / gk '), Finax (ml / qh )} values of the mass-to-charge ratio function of dissociated charged fragments of the mass spectrometer used, corresponding to maxima of occurrences of possible pairs of dissociation mass peaks produced by possible pairs of mass-dissociated charged fragments on charge {(mk / gk>), (ml / qr)}, likely to come from the dissociation of identical primary ions with the same mass-to-charge ratio (M / Q). The relationship between the primary mass M and the possible mass pairs of the charged fragments (mk, ml) is: M = mk + m ~. In the case of multicharged primary ions that dissociate directly into a pair of charged fragments, the relationship between the primary charge Q and the possible charge pairs of the charged fragments (qk ', q>) is: Q = qk, + qr.

  In the case of multicharged primary ions dissociating into pairs of neutral fragments and charged with ionization of the neutral fragments, we have: Q + e = qk, + qr • In the case of mono-charged primary ions dissociating into pairs of neutral and mono fragments charged with ionization of the neutral fragments we have: Q = qk> = qr = e. The number of correlation laws per primary mass peak is equal to the number of electrical charge distribution possibilities between the dissociated charged fragment pairs. In the case of mono-charged primary ions dissociating into pairs of neutral and mono ion-charged fragments with ionization of the neutral fragments, there is only one possibility of possible charge distribution between the dissociated charged fragment pairs namely: qk , = e and qr = e, and thus a single corresponding correlation law giving all the possible pairs of mass of charged fragments (mk, m,). For multicharged ions directly dissociating into pairs of charged fragments, with Q = 2 e, there is also only one possibility of possible charge distribution between the dissociated charged fragment pairs: qk, = e, qr = e, and therefore also a single corresponding correlation law. For Q = 3 e, there are two possible load distribution possibilities between the charged fragment pairs: (qk, = e, qr = 2 e), and (qk = 2 e, qr = e), and therefore two corresponding correlation laws.

  For Q = 4 e, there are three possible load distribution possibilities between the charged fragment pairs (qk, = e, qj '= 3e), (qk' = 3e, q1 = e), and (qk '= 2e , qr = 2e), and thus three corresponding correlation laws. And so on. In the case of multicharged primary ions dissociating into pairs of neutral and neutral ionically charged fragments, for Q = 2 e, there are two possible possible charge distribution possibilities between the charged fragment pairs: (qk '= e, qr = 2 e), and (qk '= 2 e, q1' = e), and thus two corresponding correlation laws. For Q = 3 e, there are three possible load distribution possibilities io between the charged fragment pairs (qk '= e, qi' = 3e), (qk '= 3e, qi' = e), and (qk ' = 2e, qi '= 2e), and thus three corresponding correlation laws. And so on. With the dissociation of the primary ions at low kinetic energy, the function F (m / q) of the mass spectrometer used (3) is of the form: F (m / q) = G x (m / q), where G is a function that depends on the mass spectrometer used independent of the mass-to-charge ratio of the ions, and m / q is the mass-to-charge ratio of the dissociated charged fragments. Each of the correlation laws corresponding to each pair of charges (gk ', gr) of each of the primary mass peaks corresponding to primary ions of the same mass-to-charge ratio (M / Q), dissociating into charged fragment pairs can then be always be written in the form of a linear equation: FinaX (mk / qk ') = FinaX (M / gk') ù (qk '/ qr) FinaX (mi / qr), with: FinaX (M / qk') ) = (Q / qk ') Finax (M / Q) • Each correlation laws of each primary mass peak corresponding to each charge pair of the dissociated fragments (gk', gi ') can therefore be determined by the method according to the invention simply with the values of the primary charge Q and the function Finax (M / Q) corresponding to the maximum occurrence of said primary mass peak. Indeed, the determination of the primary charge Q of each primary mass peak in the preceding step makes it possible to determine each possible charge pair (qi>, q ;,) of each correlation law of this primary mass peak for each dissociation channel possible. Determining the flight time of the maximum occurrence Finax (M / Q) and the primary charge Q of each primary mass peak in the previous step, also makes it possible to determine each value F (M / gk ') of each correlation law corresponding to this primary mass peak by: F (M / gk) = (Q / qk ') Fä, ax (M / Q •

  In step (e), primary ions of low kinetic energy are dissociated (2) so as to obtain for each of them a pair of charged fragments.

  Then in step (f), the dissociated charged fragments are injected into the mass spectrometer (3), and then, as a function of the variation of the function F (m / q) of the mass spectrometer used (3), the occurrences (or the intensity of the ion current), dissociated charged fragments detected by the ion detector (4). The function F (m / q) is of the form: F (m / q) = G x (m / q), where G is a function which depends on the mass spectrometer used (3) independent of the mass-to-charge ratio of ions, and (m / q) is the mass-to-charge ratio of the dissociated charged fragments. Then, on the basis of these measurements, without primary mass selection, the dissociation mass spectrum (MS-MS) containing all the dissociation mass peaks of each of the parent primary ion dissociation spectra of each peak of primary mass of the primary mass spectrum. The dissociation mass peaks of the different dissociation spectra corresponding to the different primary mass peaks are therefore mixed in the dissociation spectrum produced without primary mass selection. According to the usual graphical presentation in mass spectrometry, conventionally used by those skilled in the art (but not limiting), the dissociation mass spectrum (MS-MS) obtained is generally represented with two perpendicular axes, with the abscissa values measured from the function F (m / q), and ordinate the corresponding occurrences. FIG. 4 shows, by way of illustration and non-limiting example, a dissociation spectrum (MS-MS) containing the dissociation peaks corresponding to the charged pair pair dissociation channel, of the three primary mass peaks of the example of Figure 3. It is understood that in reality, the dissociation of the primary ions produces charged fragments from the other possible channels of dissociation (for example in the case of multicharged primary ions charged fragments from dissociation events in pairs of neutral and charged fragments without ionization of neutral fragments, or into three or more fragments). The multicharged ion sources also generally produce mono-charged primary ions that can dissociate into neutral and mono-charged fragment pairs without ionizing the dissociated fragments.

  Part of the neutral fragments of neutral and mono charged pair-pair dissociation events, in the case of mono-charged ion sources with neutral fragment ionization, will not be ionized. The dissociation spectrum obtained without primary mass selection will therefore also contain, in addition to the dissociation mass peaks of interest, dissociation mass peaks corresponding to these other possible dissociation channels, as well as the primary mass peaks of the ions multicharged and / or mono-charged non-dissociated primers. These other dissociation peaks, which are eliminated by the method according to the invention, and the primary mass peaks, are not shown in FIG. 4 to simplify the description.

  It can be seen in this example that the dissociation spectrum comprises fourteen dissociation mass peaks corresponding to seven pairs of dissociation peaks, each peak dissociation pair being produced by charged fragment pairs from the primary ion dissociation. identical to the same mass-to-charge ratio. In step (g) each Finax (m / q) value of the mass-to-charge ratio function of the dissociated charged fragments of the mass spectrometer used corresponding to the maximum of occurrences is determined. of each of the dissociation peaks of the dissociation spectrum obtained without primary mass selection.

  Four of the values Fmax (m / q) of the function of the mass-to-charge ratio of the dissociated charged fragments of the mass spectrometer used corresponding to the maxima of occurrences of four peaks of the earth can also be seen in the example of FIG. dissociation among the fourteen different dissociation peaks represented. In step (h), all the potential pairs are produced from the measured values of the mass-to-charge ratio function of the dissociated charged fragments of the mass spectrometer used corresponding to the maxima of occurrences of the dissociation peaks. Finax (mr / gr '), Finax (ms / qs')} of these values. The total number of potential pairs for n measured values is therefore n2.

  In step (i), we identify among the set of potential pairs {Finax (mr / gr '), Finax (ms / qs ^)}, the real pairs {Finax (mt / gt), Finax (m / corresponding to the actual pairs of dissociation peaks produced by dissociated charged fragment pairs from the dissociation of identical primary ions of same mass-to-charge ratio, for each of the primary mass peaks, by comparing the potential pairs ( Finax (mr / qr '), Finax (ms / qs')}, to the possible pairs {Finax (mk / qk'), Finax (mi / gr)} determined by the correlation laws of each of the primary mass peaks . According to the invention, this identification step consists in selecting from the potential pairs {Finax (mr / gr '), Finax (ms / qs')} those that satisfy a proximity criterion with respect to the possible pairs {Finax (mk / qk>), Finax (ml / ql>)} provided by said correlation laws of each of the primary mass peaks. This proximity criterion is of the order of the precision of the measurement of the Finax values (M / Q) of the mass-to-charge ratio function of the primary ions of the mass spectrometer used corresponding to the maximum of occurrences of the different peaks of primary mass and which determines the accuracy of the corresponding correlation laws, and the accuracy of the measurements of the Finax values (m% q) of the mass-to-charge ratio function of the dissociated charged fragments of the mass spectrometer used corresponding to the maximum of occurrences different peaks of mass dissociation and which determines the accuracy of the potential and actual pairs. The accuracy of the measurements of the Fmax (M / Q) values of the Finax values (m / q) depends essentially on the resolution of the corresponding mass peaks.

  Finally, in a step (j), each dissociation mass spectrum corresponding to each of the primary mass peaks with the actual identified pairs (Finax (mt / gt), Finax (mu / q)) is determined by positioning the pairs of corresponding dissociation mass peaks in each of the dissociation spectra of each primary mass peak. According to the usual graphical presentation in mass spectrometry conventionally used by those skilled in the art (but not limiting), each dissociation mass spectrum is generally represented with two perpendicular axes, with the values of the function F on the abscissa (m / m). q) measured, and ordinate the corresponding occurrences. FIG. 5 illustrates, by way of nonlimiting example, the three dissociation spectra of the three primary mass peaks of FIG. 3, obtained with the method according to the invention, from the dissociation spectrum without primary mass selection. of Figure 4, after the identification of the different pairs of dissociation mase peaks with the method according to the invention. In order to explain step (i) mentioned above, its preferred embodiment will now be described by reasoning on a graphical representation. Those skilled in the art will understand, however, that it is only one type of representation among others, intended primarily to illustrate the principles of this step and to understand how digital processing according to the invention are made.

  Step (i) of the method according to the invention is carried out with the following sub-steps: First, one identifies among the set of potential pairs {Finax (mr / gr '), F ,,, ax (ms / gs')}, each real pair {Fmax (mt / gt), Finax (mu / qu)) starting by generating, according to a step (i 1), a two-dimensional spectrum. This spectrum has two identical dimensions each representing the measured values of the mass-to-charge ratio function of the dissociated charged fragments of the mass spectrometer used corresponding to the maximums of occurrences of dissociation mass peaks of the dissociation spectrum obtained without selection. primary mass. Graphically, the two dimensions correspond to two axes which are preferably perpendicular to each other. We associate with each potential pair {Finax (mr / gr '), Finax (ms / qs')} a position of occurrence Prs corresponding in the two-dimensional spectrum. At each potential pair {Finax (m / gr)), Finax (ms / qs')} corresponds to a symmetric potential pair {Finax (ms / gs'), Finax (mr / gr ')} to these two potential symmetrical pairs therefore correspond a pair of positions of symmetrical different occurrences (Prs, Psr) in the plane {Finax (mr / gr '), Finax (ms / qs')} of the two-dimensional spectrum. If the number of potential pairs is n2, n2 corresponding different occurrence positions Prs are produced in the {Finax (mr / gr '), Finax (ms / qs')} plane of the two-dimensional spectrum. In the plane {Finax (mr / gr '), Finax (ms / qs')} of the two-dimensional spectrum, each correlation law is represented by a characteristic line whose position, in a step (i2), in the abovementioned plane is determined by the linear equation: Finax (mk / qk ') = Finax (M / gk') û (qk '/ qr') Finax (mi / qi '), with: Finax (M / qk') = ( Q / qk ') Finax (M / Q). We can then determine graphically in the plane Finax (mr / gr '), Finax (ms / qs')} of the two-dimensional spectrum each characteristic line with the values of each pair {Finax (M / gk'), Finax (M / gI ')}.

  Each pair {Finax (M / gk '), Finax (M / gi')} are the two points on each of the two axes of the {Finax (mr / gr '), Finax (ms / qs')} plane of the two-dimensional spectrum. (Finax (M / gk ') on the axis Frnax (mr / q,'), and Finax (M / gl ') on the axis Finax (ms / qs,)), of the equation characteristic line: Finax (mk / qk ') = Finax (M / qk') (qk '/ gr) Finax (mi / qi'). We therefore simply determine each characteristic line in the plane {F, ax (mr / gr '), Finax (ms / gs')} of the two-dimensional spectrum corresponding to each correlation law by connecting the two points Finax (M / gk') , and F ,,, ax (M / gi ') located on both axes of the two-dimensional spectrum.

  The values of each pair {Finax (M / gk '), Finax (M / gi')} of each characteristic line corresponding to each pair of charge (gk ', gi') are determined with the value Fmax (MIQ) of the function of the mass-to-charge ratio of the primary ions of the mass spectrometer used corresponding to the maximum number of occurrences and the primary charge Q, of the corresponding primary mass peak with: Finax (M / qk ') = (Q / gk') Finax (M / Q) and Finax (M / qi ') = (Q / qi') Finax (M / Q). FIG. 6 shows, by way of nonlimiting example, the characteristic lines in the plane {F 1, ax (m 1 / gr 1), F 1 × x (ms / gs')) of the two-dimensional spectrum, determined by the correlation laws corresponding to three primary mass peaks of multicharged primary ions dissociating directly into pairs of charged fragments, respectively of primary charge Q '1 = 2 e, Q'2 = 3 e, and Q'3 = 4 e.

  The equation of the characteristic line in the {F ,,, ax (mr / gr '), Finax (ms / qs')} plane of the two-dimensional spectrum of FIG. 6 corresponding to the correlation law of the primary mass peak of primary electric charge Q 'l = 2 e is: Finax (mk / e) = Finax (M' 1 / e) - Finax (mile). The equations of the two characteristic lines in the plane {F ,,, ax (mr / gr - '), Finax (ms / qs')} of the two-dimensional spectrum of FIG. 6 corresponding to the two correlation laws of the primary mass peak of primary electric charge Q'2 = 3esont: F. (mk / e) = Fin. (M'2 / e) ù 2 F ,,, ax (mi / 2e), and Fmax (mk / 2e) = Fmax (M'2 / 2e) ù (1/2) Fmax (mi / e). The equations of the three characteristic lines in the plane {Finax (mr / gr '), Finax (ms / qs •)} of the two-dimensional spectrum of FIG. 6 corresponding to the three laws of correlation of the primary mass peak of primary electric charge 5 Q '3 = 4 are: Finax (mk / e) = Fmax (M'3 / e) ù 3 Fmax (mi / 3e), Finax (mk / 3e) = Fmax (M'3 / 3e) ù (1/3) Finax (mile), and Fmax (mk / 2e) = Fmax (M'3 / 2e) to Finax (mi / 2e). In step (i4), each real pair {Finax (mt / gt), Finax (mu / qa)} among potential pairs {Finax (mr / gr '), Finax (ms / qs')} is identified in step (i4). , retaining those whose pair of corresponding occurrence positions (Ptu, Pt) in the two-dimensional spectrum, are each at a distance from one of the given characteristic lines, less than a given threshold. The value of this distance threshold is of the order of the precision of the measurements of the Finax values (M / Q) which determine the accuracy of the corresponding characteristic lines, and of the order of the precision of the measurements of the values Fmax (m / q) which determine the accuracy of the positions of potential and actual occurrences in the two-dimensional spectrum. FIG. 7 shows, by way of nonlimiting example, a plane {Finax (mr / gr '), Finax (ms / qs')} of two-dimensional spectrum in which the three characteristic lines corresponding to the correlation laws of three peaks are positioned. of primary masses of doubly charged primary ions directly dissociating into pairs of mono fragments loaded respectively with mass-to-charge ratios (M1 / Q1), (M2 / Q2), and (M3 / Q3) (with Q1 = Q2 = Q3) = 2 e), of the primary mass spectrum example of Figure 3.

  We can also see, in this nonlimiting example, and to simplify the description, that only four values, {Fmax (m1 / g1), Finax (m4 / q4)} and {Finax (milgl), Finax (m4 / q4) )}, corresponding to two real pairs of dissociation peaks among the fourteen of Figure 4, are shown.

  These four Finax values (m / q) will produce sixteen different occurrence positions Prs corresponding to the potential pairs in the {Finax (mr / gr '), Finax (ms / qs.)) Plane of the two-dimensional spectrum of FIG. which are represented by crosses.

  In the case where the fourteen values Fmax (m / q) corresponding to the fourteen dissociation peaks of FIG. 4 would be represented in FIG. 7, 196 potential occurrence positions would be determined. The two pairs of actual occurrence positions to be identified (P14, P41) and (P23, P32) are shown in Figure 7 by crosses surrounded by a circle.

  It can be seen that the pair of positions of potential occurrences closest to the characteristic line corresponding to primary ions of mass-to-charge ratio (M1 / Q1) is the pair (P14, P41). Indeed, these positions are located on or in the immediate vicinity of this characteristic line.

  The pair {Finax (mi / gi), Finax (m4 / q4)} corresponding to the pair of positions (P14, P41) is therefore identified as that of a pair of dissociation peaks belonging to the dissociation spectrum of the peak of primary mass of charge to mass ratio (M1 / Q1) of the example of FIG. 3. On the other hand, the other pairs of potential positions are remote from this characteristic line by a distance greater than the chosen threshold, so that one consider that they do not come from pairs of dissociation peaks belonging to the dissociation spectrum of the primary mass peak of charge mass ratio (M1 / Q1). It is likewise noted that the pair of positions of potential occurrences closest to the characteristic line corresponding to primary ions of mass to charge ratio (M2 / Q2) is the pair of positions (P23, P32). The pair {Finax (m2 / g2), Finax (m3 / q 3)} corresponding to the pair of positions (P23, P32) is therefore identified as that of a pair of dissociation peaks belonging to the peak dissociation spectrum. primary mass-to-charge ratio (M2 / Q2) of the example of FIG.

  The other pairs of potential positions are too far from the characteristic lines, with respect to the selected distance threshold criterion, so that they are not considered to have originated from the dissociation of primary ions of charge mass ratio (MI / QI), (M2 / Q2), and (M3 / Q3).

  To avoid unnecessarily burdening the present description, the previous example 5 illustrated in Figures 4 and 7, has only dissociation peaks of parent primary ions dissociating into pairs of charged fragments. In fact, the dissociation spectrum obtained without primary mass selection will therefore also contain mass peaks corresponding to other possible dissociation channels of the multicharged and / or mono-charged primary ions, as well as the primary mass peaks of the primary ions. multicharged and / or mono charged non dissociated. These other dissociation peaks will produce additional potential pairs. These potential pairs are for the most part eliminated by the criterion of identification of real pairs. But some of these potential pairs may be accepted by the identification criterion, and produce actual identified false pairs, which will produce false pairs of dissociation peaks in dissociation spectra eventually produced by the method of the invention. Those skilled in the art will be able to eliminate these false peaks of dissociation mass by comparing the corresponding mass values of the pairs of fragments corresponding to these false peak pairs to the masses of the fragment pairs of the possible theoretical dissociation channels of the parent molecule.

  The invention as described in the foregoing has been explained by a graphical approach involving a two-dimensional space. However, it is understood that its concrete implementation is typically performed by a digital computer such as a DSP (Digital Signal Processor) executing the appropriate programs. In particular, the characteristic lines will typically be digital data (equations or sets of coordinates) with which the digital data produced by the spectrometers and supplied to the calculator will be compared.

  More concretely, the present invention can be implemented in the form of a software module in addition to existing mass spectrometry equipment, and interfaced with the other software of this equipment so as to ensure essentially the establishing the characteristic line data and collecting the measured data to confront these feature line data.

  In any case, one skilled in the art will understand that the production of the primary mass spectrum and the dissociation spectra from multicharged and / or mono-charged primary ions dissociating into pairs of charged fragments gives the possibility of identifying the studied molecules. It will be understood in this regard that the production of dissociation spectra containing only mass peaks corresponding only to the dissociation channels in pairs of charged fragments will facilitate their identification.

  The dissociation of primary ions into pairs of charged fragments of kinetic energy can be achieved by the technique of collision induced with the molecules of an inert gas CID / CAD (acronym for "Collision Induced Dissociation / Collision Activated Dissociation"), by the collision technique with a Surface Induced Dissociation (SID) surface, by the ECD (Electron Capture Dissociation) electron capture technique, by the IRMPD infrared photon ionization technique ( acronym for "Infra Red Multi Photon Dissociation"), by the technique of high energy PD photons (acronym for "Photo Dissociation"), by the technique of high energy photons PD (acronym for "Photo Dissociation"), by the technique BIRD 25 (acronym for "Black Body Infra Red Dissociation"), or any other technique for fragmenting primary ions into charged fragment pairs. In the case of the dissociation of ECD-electrically-charged primary ions, electron capture inducing fragmentation modifies the charge of the primary ion Q before dissociation. In this case the relation between the primary charge Q and the possible charge pairs of the charged fragments (gk ', gr) is: Q-e = qk' + qr.

  The object of the invention is also to propose a tandem mass spectrometer, illustrated by way of non-limiting example in FIG. 2, comprising, according to the general direction of movement of the ions: a source of ions (1), means for supplying a primary mass spectrum of these primary ions from these ionized molecules, so as to be able to identify the value of the F, 1ax (M / Q) function of the mass-to-charge ratio of the primary ions of the spectrometer of mass used corresponding to the maximum number of occurrences and the primary electric charge Q, corresponding to each primary mass peak of these ions, - a device for dissociating (2) the primary ions so as to obtain, for each of them, a pair of charged fragments, - a mass spectrometer (3), producing the primary mass spectrum of the primary ions, and the dissociation spectrum without primary mass selection of the dissociated charged fragments, - an ion detector (4), - means of identification ication, in the set of dissociation mass peaks, pairs of dissociation mass peaks corresponding to pairs of charged fragments resulting from the dissociation of parent primary ions having the same mass-to-charge ratio, these identification means being arranged so that the identification is based on the measured values F ,,, ax (m / q) of the mass-to-charge ratio function of the dissociated charged fragments of the mass spectrometer used corresponding to the maxima of occurrences of the mass peaks of the dissociation, and predetermined laws, called correlation, giving the possible pairs of these values.

  Most ion sources produce, in addition to primary ions of interest primary mass peaks of the molecules to be identified, a quasi-continuous background of ions between primary mass peaks called chemical noise.

  This chemical noise also present in the dissociation spectrum produced without primary mass selection in step (f) of the process according to the invention can mask small peaks of dissociation of interest. To eliminate substantially all of this chemical noise from the dissociation spectrum produced without primary mass selection, a device may be used to select only all the primary ions from the primary mass peaks prior to their injection into the paired dissociation device (2). loaded fragments. The purpose of the invention is therefore also to propose a tandem mass spectrometer, which is illustrated by way of nonlimiting example in FIG. 8, comprising, according to the general direction of movement of the ions: an ion source (1) means for supplying a primary mass spectrum of these primary ions from these ionized molecules, so as to be able to identify the Finax value (M / Q) of the mass-to-charge ratio function of the primary ions of the spectrometer of used mass corresponding to the maximum number of occurrences and the primary electric charge Q, corresponding to each primary mass peak of these ions, - an ion trap (5) for storing the ions emitted by the ion source (1) before their injection into the device for dissociating the primary ions in pairs of charged fragments (2), means for injecting into the device for dissociating the primary ions into pairs of charged fragments (2), only the primary ions originating from the peaks of primary mass of the molecules to be identified; - a device for dissociating the primary ions into pairs of charged fragments (2); - a mass spectrometer (3), producing the primary mass spectrum of the primary ions, and the dissociation spectrum without primary mass selection of dissociated charged fragments, an ion detector (4). means for identifying, in the set of dissociation mass peaks, pairs of dissociation mass peaks corresponding to pairs of charged fragments resulting from the dissociation of parent primary ions having the same mass-to-charge ratio, these means of identification being arranged so that the identification is based

  31 on the measured values Finax (m / q) of the mass-to-charge ratio function of the dissociated charged fragments of the mass spectrometer used corresponding to the maxima of occurrences of the dissociation mass peaks, and of predetermined correlation laws, giving the possible pairs of these values.

  The preferred but non-limiting aspects of the tandem mass spectrometers shown in FIGS. 2 and 8 are as follows: the source of primary ions (1) is a source of multicharged and / or mono-charged ions, the device for dissociation (2) of the primary ions in pairs of charged fragments is equipped with a system that ionizes the neutral fragments originating from the dissociation at low kinetic energy of the primary ions. The ionization of the neutral fragments originating from the dissociation of the primary ions in the dissociation device (2) makes it possible to apply the method according to the invention not only to the mono-charged primary ions dissociating in pairs of neutral and mono charged fragments, but also to other multicharged primary ion dissociation channels dissociating into neutral and charged fragment pairs. In both cases, each charged and neutral pair of fragments becomes a pair of charged fragments after ionization of the neutral moiety in the dissociation device (2). The dissociation channels of the multicharged primary ions concerned, if we denote M and Q respectively the mass and the electric charge of the parent primary ion and mi and qi the mass and the charge of each dissociated fragment i (with i = 1 , 2) with mi + m2 = M, are the following: M (Q) -> mi (g1 = Q + e) + m2 (q2 = 0) û * mi (g1 = Q + e) + m2 (q2 = e), and M (Q) û * mi (qi = Q) + m2 (q2 = 0) û * mi (qi = Q) + m2 (q2 = e). In the case of dissociation by the Electron Capture Dissociation ECD electron capture technique, the ionization system of the dissociated neutral fragments in the dissociation device (2) will allow this dissociation technique to be applied to the primary ions. mono charged, because the pair of neutral fragments which is then produced can be ionized in the dissociation device (2) by this system.

  Preferred but non-limiting aspects of the tandem mass spectrometers shown in FIGS. 2 and 8 are as follows: the dissociation device (2) producing the dissociated charged fragment pairs is an ion trap containing gas dissociating the primary ions at low kinetic energy by multiple collisions with the gas molecules, - the ion trap (2) is equipped with an ionizing system for the neutral fragments 10 from the low kinetic energy dissociation of the primary ions in the trap with ions (2). The ion trap forming the dissociation device (2), for primary ions, or dissociated charged fragments, of the same mass-to-charge ratio previously selected with the mass selection mode of the ion trap, produces pairs of charged fragments, by performing two successive steps of dissociations by collision with gas molecules and neutral fragment ionizations, without primary mass selection of the dissociated charged fragments produced at each of the two steps.

  The use of the ion trap (5) to eliminate, by multiple selection of the primary mass peaks, the chemical noise between the primary mass mass peaks in the dissociation spectrum produced without primary mass selection, also makes it possible to if necessary, eliminate the primary ions, and therefore the corresponding dissociation peaks in the dissociation spectrum produced by the process according to the invention, from the primary mass peaks of the molecules identified by the primary mass spectrum.

  Preferred but non-limiting aspects of the tandem mass spectrometers, shown in FIGS. 2 and 8, are as follows: the device for dissociation (2) of the primary ions into pairs of charged fragments at low kinetic energy is a guide to Multipolar wave containing gas dissociating the primary ions by multiple collisions with the gas molecules, the multipole waveguide is equipped with a system ionizing the neutral fragments from the low kinetic energy dissociation of the primary ions in the multipole waveguide (2).

  Components and operation of spectrometers according to the invention

  The components and operation of a tandem mass spectrometer employing the spectrometric method according to the invention will now be described in more detail and by way of example only. The ion source (1) can be continuous or pulsed. It may be one of the following ion sources or any other type of multicharged and / or mono-charged ion source: a multi-charged electrospray ion source ESI (acronym for "Electro-Spray Ionization"), a MALDI pulsed ion source (acronym for "Matrix Assisted Laser Desorption Ionization"), a source of atmospheric pressure chemical ionization ions APCI (acronym for "Atmospheric Pressure Chemical Ionization"), a photo ion source atmospheric pressure ionization APPI (acronym for "Atmospheric Pressure Photo Ionization"), a laser desorption ionization ion source (LDI) (acronym for "Laser Desorption Ionization"), an inductively coupled plasma ion source ICP (Acronym for "Inductively Coupled Plasma"), an electron impact ion source EI (acronym for "Electron Impact"), a CI ionization ion source (acronym for "Chemical Ionization"), a source of ions ionization F field I (acronym for "Field Ionization"), an ion source by bombarding a target with a neutral atom beam FAB (acronym for "Fast Atom bombing"), an ion source by bombarding a target with an LSIMS ion beam (acronym for "Liquid Secondary Ion Mass spectrometry"), an atmospheric pressure ionisation ion source API (acronym for "Atmospheric Pressure Ionization"), a field desorption ion source FI (acronym for "Field Desorption"), and a source of ion desorption ionization on DIOS silicon (acronym for "Desorption Ionization On Silicon").

  The dissociation system (2) can be a multipole waveguide containing gas allowing the induced collision dissociation CID (acronym for "Collision Induced Dissociation") by multiple shocks at low kinetic energy with a gas, an ion trap allowing induced collision cleavage (Collision Induced Dissociation) or electron capture ECD (Acronym for "Electron Capture Dissociation"), a Fourier transform mass spectrometer for induced collision dissociation CID (acronym for "Collision Induced Dissociation") or electron capture ECD (acronym for "Electron Capture Dissociation"), or any device for fragmenting primary ions to produce pairs of charged fragments.

  The dissociation system (2) may be equipped with a device for ionizing the neutral fragments produced by the dissociation of the primary ions into pairs of neutral and charged fragments. The device for ionizing the neutral fragments produced by the dissociation of the primary ions into pairs of neutral fragments and loaded into the dissociation system (2) may be: an electron impact ionisation device, a laser ionization device , or any other type of ionization device for ionizing the neutral fragments in the dissociation system (2). The ion trap (5) used to inject the primary ions of the primary mass peaks to the dissociation device (2), and to remove the ions from the chemical noise emitted by the ion source (1), can be: a hatch hyperbolic geometry 3D ion beam, a cylindrical geometry linear 2D ion trap, or any other type of ion trap. The mass spectrometer (3) used to produce the primary mass spectrum and the dissociation spectrum without primary mass selection may be: a time-of-flight mass spectrometer, a sector mass spectrometer

  Magnetic field, a quadrupole mass spectrometer, an ion trap, a Fourier transform mass spectrometer, or any other type of mass spectrometer. The flight time space of the time-of-flight mass spectrometer (3) between the pulsation of the ion packet and the ion detector (4) may be linear, or equipped with a reflectron. The reflectron used may be: one-stage, two-stage, curved-field CFR (acronym for "Curved Field Reflectron"), quadratic, or any other type of reflectron. The ions produced by the ion source (1) can be stored to produce the pulsation of the ion pack in an ion trap, or by any other ion storage system. The pulsation of the ion packet may be located in the ion source (1), between the ion source (1) and the dissociation device (2), or between the dissociation device (2) and the ion source (1). ion detector (4). The pulsation of the ion packet for a continuous ion source can be achieved: by scanning the continuous ion beam through a slot, by a variable electric field applied between two deflection plates, by the known injection technique orthogonal by applying a variable electric field between two electrodes in the direction perpendicular to the ion beam, or by any other pulsation device of a continuous ion beam. The ion trap (3) can be: a hyperbolic geometry 3D ion trap, a cylindrical geometry linear 2D ion trap, or any other type of ion trap. Four non-limiting embodiments of mass spectrometers will now be described based on the use of the components illustrated in FIG. 2 and FIG. 8. First Embodiment of a Spectrometer

  The first embodiment of a tandem mass spectrometer according to the invention is illustrated in FIG. 2. It comprises successively, according to the general direction of movement of the primary ions, a source of ESI electrospray multi-charged ions (1) ( acronym for "Electro-Spray Ionization"), a dissociation device (2) consisting of a multipole waveguide (q) containing gas generating, by CID (acronym for "Collision Induced Dissociation") at low kinetic energy. dissociation the primary ions, a mass spectrometer (3) quadrupole (Q), and an ion detector (4). This tandem mass spectrometer embodiment is known to those skilled in the art who use tandem mass spectrometers with Qi-q-Q2 triple quadrupole mass selection. The first embodiment is identical to these devices with the elimination of the first quadrupole Q1 which is used, by the skilled person, in MS-MS mode for the selection of primary mass in the existing triple quadrupole.

  The primary mass spectrum is first produced with the quadrupole Q, without dissociation in the multipole waveguide q. Then, the dissociation mass spectrum is produced without primary mass selection also with the quadrupole Q, after the dissociation of the primary ions into pairs of charged fragments in the multipolar waveguide by CID (acronym for "Collision Induced Dissociation"). at low kinetic energy. The pairs of dissociation mass peaks of each of the dissociation spectra corresponding to each primary mass peak are identified with the method according to the invention. Each dissociation spectrum is finally produced with the identified pairs of dissociation mass peaks.

  In a variant of the first embodiment which has just been presented, the ion source (1) may be preceded by a device for separating the molecules by LC liquid chromatography acronym for Liquid Chromatography.

  Second embodiment of a spectrometer30

  The second embodiment of a tandem mass spectrometer according to the invention is illustrated in FIG. 2. It comprises successively, according to the general direction of movement of the primary ions, a source of ions (1) multi-charged with electrospray ESI acronym Electro-Spray Ionisation, a cylindrical geometry 2D linear ion trap (2) (3), and an ion detector (4). In this embodiment the ion trap is used both as a dissociation device (2) and as a mass spectrometer (3). This tandem mass spectrometer embodiment is known to those skilled in the art which uses identical mass spectrometers to produce primary mass selection dissociation mass spectra. The primary mass spectrum is first produced with the ion trap (2) (3) after storage of the primary ions emitted by the ion source (1), without dissociation. Then, with the ion trap, the dissociation mass spectrum is produced without primary mass selection, after the dissociation of the primary ions into pairs of CID-charged fragments (acronym for "Collision Induced Dissociation") at low kinetic energy with the molecules. a neutral gas in the volume of the hatch. The pairs of dissociation mass peaks of each of the dissociation spectra corresponding to each primary mass peak are then identified with the method according to the invention. Each dissociation spectrum is finally produced with the identified pairs of dissociation mass peaks.

  In a variant of the second embodiment which has just been described, the ion source (1) may be preceded by a device for separating the molecules by LC liquid chromatography acronym for Liquid Chromatography.

  In another variant of the second embodiment which has just been presented, the linear 2D ion trap is replaced by a hyperbolic geometry 3D ion trap. 30

  In another variant of the second embodiment which has just been presented, the ion trap (2) (3) is equipped with a device for ionizing the neutral fragments produced by the dissociation of the ions in the trap. This device can be an electronic impact ionization system or a pulsed or continuous laser ionization system. This device will make it possible to use the method according to the invention in MS 'mode. After realizing the dissociation spectrum (MS-MS = MS2) without primary mass selection with the dissociation of primary ions by CID (acronym for "Collision Induced Dissociation") at low kinetic energy, and the ionization of dissociated neutral fragments, a second dissociation spectrum (MS3) of the dissociated charged fragments can be produced. We start by storing the primary ions emitted by the ion source (1) in the ion trap (2) (3), then we select the primary ions corresponding to a single primary mass peak, eliminating the other primary ions in the manner known to those skilled in the art of primary mass selection of the ion trap (2) (3) used. The primary ions selected by CID (acronym for "Collision Induced Dissociation") are dissociated at low kinetic energy and the dissociated neutral fragments are ionized and then the charged fragments are dissociated in a second step without primary mass selection. dissociated in the first step, by CID (acronym for "Collision Induced Dissociation") at low kinetic energy and ionizes the dissociated neutral fragments. The dissociation spectrum (MS3) of dissociated charged fragments is finally produced in the second step without primary mass selection. Then, the pairs of dissociation mass peaks corresponding to each dissociation spectrum (MS3) of each dissociation mass peak of the selected primary mass peak are identified. Each dissociation mass spectrum (MS3) is finally produced with the identified pairs of dissociation peaks. The foregoing steps can be repeated to produce the dissociation mass (MS) spectra without primary mass selection of any selected dissociation mass peak (MSn-2).

  In another variant of the second embodiment which has just been presented, illustrated by FIG. 8, the ion trap (2) (3) is preceded by a second ion trap (5) for injecting only the ions primary primary peaks in the second ion trap (2) (3), and eliminate the chemical background of the ion source (1) of the dissociation spectrum (MS-MS) produced without primary mass selection by the second ion trap (2) (3).

  Third Embodiment of a Spectrometer The third embodiment of a tandem mass spectrometer according to the invention is illustrated in FIG. 2. It comprises, successively, according to the direction of general displacement of the primary ions, an ion source ( 1) electrospray electrospray ESI acronym for Electro-Spray Ionisation, a 3D hyperbolic geometry linear ion trap (2), a reflectron time-of-flight mass spectrometer (3), and an ion detector (4). In this embodiment the ion trap (2) is also used to pulse each ion packet to produce the flight time. This tandem mass spectrometer embodiment is known to those skilled in the art which uses identical mass spectrometers to produce primary mass selection dissociation mass spectra. The primary mass spectrum is first produced with the time-of-flight mass spectrometer after storage of the primary ions emitted by the ion source (1), without dissociation, and the pulsation of the ion packet towards the flight time space. Then, in a second acquisition, one dissociates without selection of primary mass by CID (acronym for "Collision Induced Dissociation") at low kinetic energy with the molecules of a neutral gas in the volume of the ion trap (2), in pairs of fragments loaded the primary ions stored in the trap. The time-of-flight dissociation mass spectrum is then produced without primary mass selection, by pulsing the ion packet containing the dissociated charged fragments. The pairs of dissociation mass peaks of each of the dissociation spectra corresponding to each primary mass peak are then identified with the method according to the invention. Each dissociation spectrum is finally produced with the identified pairs of dissociation mass peaks.

  In a variant of the third embodiment which has just been presented, the ion source (1) may be preceded by a device for separating the molecules by LC liquid chromatography acronym for Liquid Chromatography.

  In another variant of the third embodiment which has just been presented, the ion trap (2) is equipped with a device for ionizing the neutral fragments produced by the dissociation of the ions in the trap. This device can be an electronic impact ionization system or a pulsed or continuous laser ionization system. This device will make it possible to use the method according to the invention in MS 'mode. After realizing the dissociation spectrum (MS-MS = MSZ) without primary mass selection with the dissociation of the primary ions by CID (acronym for "Collision Induced Dissociation") at low kinetic energy and the ionization of the dissociated neutral fragments, a second dissociation spectrum (MS3) of the dissociated charged fragments can be produced. The primary ions emitted by the ion source (1) are first stored in the ion trap (2) (3), then the primary ions corresponding to a single primary mass peak are selected, eliminating the other ions. primary in the manner known to those skilled in the art of primary selection of the ion trap (2) (3) used. The primary ions selected by CID (acronym for "Collision Induced Dissociation") are dissociated at low kinetic energy and the dissociated neutral fragments are ionised and then again dissociated in a second step without primary mass selection. Charged dissociated in the first step, by CID (acronym for "Collision Induced Dissociation") at low kinetic energy and ionizes dissociated neutral fragments. The dissociation spectrum of the dissociated charged fragments in the second step is finally produced without primary mass selection. Then, the pairs of dissociation mass peaks corresponding to each dissociation spectrum (MS3) of each dissociation mass peak of the selected primary mass peak are identified. Each dissociation mass spectrum (MS3) is finally produced with the identified pairs of dissociation peaks. The foregoing steps can be repeated to produce the dissociation mass spectra (MSn) without primary mass selection of any selected dissociation mass peak (MSi-2).

  In another variant of the third embodiment that has just been presented, illustrated in FIG. 8, the ion trap (2) is preceded by a second ion trap (5) for injecting only the primary ions of the peaks of mass to primary in the second ion trap (2), and eliminate the chemical background noise of the ion source (1) of the dissociation spectrum produced without primary mass selection by the second ion trap (2).

  In another variation of the third embodiment just described, the electrospray multicharged ion source is replaced by a MALDI-insulated ion source (acronym for "Matrix Assisted Laser Desorption Ionization").

  Fourth Embodiment of a Spectrometer The fourth embodiment of a tandem mass spectrometer according to the invention is illustrated in FIG. 2. It comprises successively, according to the direction of general displacement of the primary ions, an ion source. (1) electrospray multi-fired ESI acronym 25 of Electro-Spray Ionization, a FTICR (2) (3) Fourier Transform Ion Cyclotron Resonance Fourier transform mass spectrometer, and a detector (4) measuring the ion cyclotron frequency . In this embodiment, the Fourier transform mass spectrometer is used both as a dissociation device (2) and as a mass spectrometer (3).

  This tandem mass spectrometer embodiment is known to those skilled in the art who uses identical mass spectrometers to produce primary mass selection dissociation mass spectra. The primary mass spectrum is first produced with the Fourier transform mass spectrometer after storage of the primary ions emitted by the ion source (1), without dissociation. Then, in a second acquisition, one dissociates without selection of primary mass by CID (acronym for "Collision Induced Dissociation") at low kinetic energy with the molecules of a neutral gas in the volume of the Fourier transform mass spectrometer (2 ) (3), in pairs of fragments to charge the stored primary ions. The Fourier transform dissociation mass spectrum is then produced without primary mass selection. The pairs of dissociation mass peaks of each of the dissociation spectra corresponding to each primary mass peak are then identified with the method according to the invention. Each dissociation spectrum is finally produced with the identified pairs of dissociation mass peaks.

  In a variant of the fourth embodiment which has just been presented, the ion source (1) may be preceded by a device for separating the molecules by LC liquid chromatography acronym for Liquid Chromatography. In another variant of the fourth embodiment which has just been presented, the Fourier transform mass spectrometer (2) (3) is equipped with a device for ionizing the neutral fragments produced by the dissociation of the ions. in the hatch. This device may be an electronic impact ionization system or a pulsed or continuous laser ionization system. This device will make it possible to use the method according to the invention in MS mode. After realizing the dissociation spectrum (MS-MS = MS2) without primary mass selection with the dissociation of primary ions by CID (acronym for "Collision Induced Dissociation") at low kinetic energy and the ionization of dissociated neutral fragments, a second dissociation spectrum (MS3) of the dissociated charged fragments can be produced. The primary ions emitted by the ion source (1) are first stored in the Fourier transform mass spectrometer (2) (3), then the primary ions corresponding to a single primary mass peak are selected, eliminating the other primary ions according to the method known to those skilled in the art of primary mass selection of the Fourier transform mass spectrometer (2) (3) used. The primary ions selected by CID (acronym for "Collision Induced Dissociation") are dissociated at low kinetic energy and the dissociated neutral fragments are ionized and then the charged fragments are dissociated in a second step without primary mass selection. dissociated in the first step, by CID (acronym for "Collision Induced to Dissociation") at low kinetic energy and ionizes dissociated neutral fragments. The dissociation spectrum of the dissociated charged fragments at the second stage is finally produced without selection of the primary mass. Then, the pairs of dissociation mass peaks corresponding to each dissociation spectrum (MS3) of each dissociation mass peak of the selected primary mass peak are identified. Each dissociation mass spectrum (MS3) is finally produced with the identified pairs of dissociation peaks. The foregoing steps can be repeated to produce the dissociation mass spectra (MSn) without primary mass selection of any selected dissociation mass peak (MSn-2). In another variant of the fourth embodiment which has just been presented, illustrated in FIG. 8, the Fourier transform mass spectrometer (2) (3) is preceded by a linear 2D ion trap (5). to inject only the primary ions of the primary mass peaks into the Fourier transform mass spectrometer (2) (3), and to eliminate the chemical background noise of the ion source (1) of the dissociation spectrum produced without primary mass selection by the Fourier Transform Mass Spectrometer (2) (3).

  In another variant of the fourth embodiment which has just been presented, the linear 2D ion trap (2) which precedes the Fourier transform mass spectrometer (3) is used as a dissociation device (2) for

  Producing the dissociated charged fragments prior to their injection into the Fourier transform mass spectrometer (3), which is only used as a mass spectrometer (3).

  In another variant of the fourth embodiment that has just been presented, the source of electrogenerated multicharged ions is replaced by a mono-charged ion source MALDI (acronym for "Matrix Assisted Laser Desorption Ionization").

  As will be understood, the present invention is not limited to the embodiment described above and shown in the drawings. In particular, the variants of each of the embodiments may be used one by one or combined with one another.

  BIBLIOGRAPHIC REFERENCES [1] J.D. Pinston et al, Rev. Sci.Instrum., 57 (4), (1983), p.583. C. G. Enke et al, US Patent 4,472,631 (1984). [2] S. Della-Negra and Y. Leybec, Anal. Chem., 57 (11), (1985), p. 2035. K. G. Standing et al., Anal. Instrumen., 16, (1987), p; 173. R.J. Conzemius US Patent 4,894,536 (1990). [3] Alderdice et al, US Patent 5,206,508 (1993). [4] R. H. Bateman, J.M. Brown, D.J. Kenny, US Patent 2005/0098721 A1 (2005). [5] C. G. Enke, patent PCT / US2004 / 008424. [6] D. Scigocki, FR Patent No. 0602920 (2006) [7] D. Scigocki, FR Patent No. 0605985 (2006) [8] R. D. Smith et al, US Patent No. 5,073,713 (1991).

Claims (10)

  A method of tandem mass spectrometry, characterized in that it comprises the following steps: (a) providing a source of primary ions to be analyzed, (b) generating a primary mass spectrum of the primary ions without dissociation, spectrum containing peaks of occurrences of primary ions; (c) from this spectrum, determine for each of the primary mass peaks it contains the value Finax (M / Q) of the mass-to-charge ratio function of the primary ions of the mass spectrometer used corresponding to the maximum of occurrences of this peak, and the electric charge Q of the primary ions, (d) from these data, determine correlation laws in the form of linear equations of each of the primary mass peaks, giving all the possible pairs { Finax (mk / gk '), Finax (mi / qr)} values of the function of the mass-to-charge ratio of the dissociated charged fragments of the mass spectrometer used corresponding to maxima of occurrences of possible pairs of mass peaks of dissociation produced by possible pairs of charged mass-on-charge {(mk / gk •), (mi / qi ^)} moieties that may originate from the dissociation of identical primary ions with the same mass to charge ratio (M / Q), (e) dissociate primal ions areas without primary mass selection, at low kinetic energy, so as to obtain for each of them, a pair of charged fragments, (f) generate a dissociation spectrum, without primary mass selection, containing the dissociation mass peaks of each of the dissociation spectra 25 corresponding to each primary mass peak, (g) from this spectrum, determine for each of the dissociation mass peaks that it contains each value Fiax (m / q) of the ratio function charge mass of the dissociated charged fragments of the mass spectrometer used corresponding to the maximum number of occurrences of this peak, (h) generating from the measured values of the function F 1 (m / q) of the mass-to-charge ratio of the fragments dissociated charges of the mass spectrometer 47 used corresponding to the maximums of occurrences of the dissociation peaks all the potential pairs (Frrax (mr / gr '), Finax (ms / gs')) of these values, (i) identify, among the said pot pairs (Finax (mr / gr.), Finax (ms / qs')}, the actual pairs {Finax (mt / gt), Finax (m / qu)) that satisfy a criterion of proximity with respect to the correlation laws, and thereby identifying the pairs of dissociation mass peaks corresponding to the same peak of the primary mass spectrum, (j) producing each dissociation spectrum corresponding to each of the primary mass peaks, with the pairs of dissociation mass peaks corresponding to the pairs actual identified {Finax (mt / gt), Finax (mä / qä)}. io   2. Method according to claim 1, characterized in that the pairs of dissociated charged fragments are derived from the dissociation at low kinetic energy of multicharged primary ions, and are also initially derived from the dissociation at low kinetic energy of primary ions multicharged in pairs of neutral and charged fragments, followed by ionization of the neutral fragments.   3. Method according to claim 1, characterized in that the pairs of dissociated mono-charged fragments are first derived from the dissociation at low kinetic energy of mono-charged primary ions in pairs of neutral and mono-charged fragments, and then ionization of neutral fragments.   4. Method according to one of claims 1 to 3, characterized in that the step (i) for identifying real pairs comprises the following sub-steps: (ii) generating a two-dimensional mass spectrum having two first 25 dimensions each representing the measured values Finax (m / q) of the mass-to-charge ratio function of the dissociated charged fragments of the mass spectrometer used corresponding to the maximum occurrences of each of the dissociation peaks, the position Prs of each occurrence of detection in the plane defined by the two dimensions corresponding to a potential pair {Finax (mr / gr '), Finax (ms / qs')} 30 of these values, 48 (i2) to position in the same plane characteristic lines determined by the equations linear of said correlation laws, (i3) positioning in this same plane the occurrences Prs corresponding to each potential pair of values, and (i4) identifying, among the potential pairs of values, cell having an occurrence position Prs, in said plane which is at a distance from one of the characteristic lines less than a given threshold, thereby identifying the actual pairs of values corresponding to actual pairs of dissociation mass peaks produced by pairs of charged fragments resulting from the dissociation of identical primary ions to ions with the same mass-to-charge ratio.   5. A tandem mass spectrometer comprising, according to the direction of general displacement of the ions: an ion source (1), means for supplying a primary mass spectrum of these primary ions resulting from these ionized molecules, so as to be able to identify the value Fmax (MIQ) of the mass-to-charge ratio function of the primary ions of the mass spectrometer used corresponding to the maximum number of occurrences and the primary electric charge Q, corresponding to each primary mass peak of these ions A device for dissociating (2) the primary ions so as to obtain, for each of them, a pair of charged fragments, - a mass spectrometer (3), producing the primary mass spectrum of the primary ions, and the dissociation spectrum without primary mass selection of charged fragments, - an ion detector (4), - identification means, in the set of dissociation mass peaks, of the pairs of dissociation mass peaks corre coupling to pairs of charged fragments resulting from the dissociation of parent primary ions of the same mass-to-charge ratio, these identification means being arranged so that the identification is based on the measured values Finax (m / q) of the function of the mass-to-charge ratio of the dissociated charged fragments of the mass spectrometer used corresponding to the 49 peaks of occurrences of dissociation mass peaks, and of predetermined correlation laws, giving the possible pairs of these values.   6. Tandem mass spectrometer comprising according to the direction of general movement of the ions: - an ion source (1), - means for supplying a primary mass spectrum of these primary ions from these ionized molecules, so as to be able to identify the value Finax (MQ) of the mass-to-charge ratio function of the primary ions of the mass spectrometer used corresponding to the maximum number of occurrences and the primary electric charge Q, corresponding to each primary mass peak of these ions, an ion trap (5) for storing the ions emitted by the ion source (1) before they are injected into the device for dissociating the primary ions into pairs of charged fragments (2); means for injecting into the ion source; device for dissociating primary ions in pairs of charged fragments (2), only the primary ions originating from the primary mass peaks of the molecules to be identified, - a device for dissociating the primary ions in pairs of fragments c hargated (2), -a mass spectrometer (3), producing the primary mass spectrum of the primary ions, and the dissociation spectrum without primary mass selection of charged fragments, - an ion detector (4). means for identifying, in the set of dissociation mass peaks, pairs of dissociation mass peaks corresponding to pairs of charged fragments resulting from the dissociation of parent primary ions having the same mass-to-charge ratio, these identification means being arranged so that the identification is based on the measured values F ,,, ax (m / q) of the function of the mass-to-charge ratio of the dissociated charged fragments of the mass spectrometer used corresponding to the maxima of occurrences dissociation mass peaks, and predetermined correlation laws, giving the possible pairs of these values.   Tandem mass spectrometer according to claims 5 and 6, characterized in that: - the source of primary ions (1) is a source of multicharged and / or mono charged ions, - the dissociation device (2) primary ions in pairs of charged fragments is equipped with a system ionizing the neutral fragments from the dissociation at low kinetic energy of the primary ions.   8. Tandem mass spectrometer according to claims 5 and 6, characterized in that: - the dissociation device (2) producing the dissociated charged fragment pairs is an ion trap, containing a low-dissociation gas kinetic energy the primary ions by multiple collisions with gas molecules, - the ion trap (2) is equipped with a system ionizing the neutral fragments from the low kinetic energy dissociation of the primary ions in the ion trap ( 2). The ion trap forming the dissociation device (2), for primary ions, or dissociated charged fragments, of the same mass-to-charge ratio previously selected with the mass selection mode of the ion trap, produces pairs of charged fragments, by performing two successive steps of dissociations by collision with gas molecules and neutral fragment ionizations, without primary mass selection of the dissociated charged fragments produced at each of the two steps. 25   9. Tandem mass spectrometer according to claims 5 and 6, characterized in that: - the device for dissociation (2) primary ions in pairs of charged fragments at low kinetic energy is a multipolar waveguide containing of the gas dissociating the primary ions by multiple collisions with the gas molecules, - the multipole waveguide is equipped with a system ionizing the neutral fragments from the low kinetic energy dissociation of the primary ions in the waveguide multipolar (2).   10. A computer program adapted to be implemented in a tandem flight time mass spectrometry system and comprising a set of instructions able to perform the following steps: (a) control the system so that it generates from a source of primary ions to be analyzed, a primary mass spectrum of these primary ions, without dissociation, this spectrum containing peaks of occurrences of primary ions, (b) perform an acquisition of the data of this spectrum (c) from said data, determine for each of the primary mass peaks it contains the value FinaX (M / Q) of the mass-to-charge ratio function of the primary ions of the mass spectrometer used corresponding to the maximum of occurrences of this peak, and the electric charge Q of the primary ions, (d) from these peak data, determine correlation laws giving all possible pairs of values of the mass-to-charge ratio function of the charged fragments. mass spectrometer partners used corresponding to maxima of occurrences of possible pairs of dissociation mass peaks produced by pairs of charged fragments from different primary ions, (e) controlling the system to cause ion dissociation to obtain for each of them, a pair of charged fragment, (f) generate, without selection of primary mass, a dissociation spectrum of these dissociated charged fragments containing the dissociation mass peaks of each of the dissociation spectra corresponding to each primary mass peak, (g) from this spectrum, determine for each of the dissociation mass peaks that it contains each Finax value (m / q) of the mass-to-charge ratio function of the dissociated charged fragments of the mass spectrometer used corresponding to the maximum number of occurrences of this peak, (h) generating from the measured values all the potential pairs {Fm x (m, / gr ') , Finax (ms / qs ^)} of these values, 52 (i) identify, among said potential pairs {Finax (mr / gr '), Finax (ms / gs')}, the actual pairs {Finax (mt / gt ), Finax (mu / qu)} that satisfy a criterion of proximity to the correlation laws, and thus identify the pairs of dissociation mass peaks corresponding to the same peak of the primary mass spectrum, (j) produce each spectrum of dissociation corresponding to each of the primary mass peaks, with the pairs of dissociation mass peaks corresponding to the actual identified pairs {Finax (mt / gt), Finax (mu / qu)}