EP1958233A1 - Analyse automatique de matrices complexes au moyen d'un spectrometre de masse - Google Patents

Analyse automatique de matrices complexes au moyen d'un spectrometre de masse

Info

Publication number
EP1958233A1
EP1958233A1 EP06828156A EP06828156A EP1958233A1 EP 1958233 A1 EP1958233 A1 EP 1958233A1 EP 06828156 A EP06828156 A EP 06828156A EP 06828156 A EP06828156 A EP 06828156A EP 1958233 A1 EP1958233 A1 EP 1958233A1
Authority
EP
European Patent Office
Prior art keywords
mass spectrometer
compound
controller
mass
analysis
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP06828156A
Other languages
German (de)
English (en)
Other versions
EP1958233A4 (fr
EP1958233B1 (fr
Inventor
Byron Kieser
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
DH Technologies Development Pte Ltd
Original Assignee
MDS Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from US11/567,281 external-priority patent/US7548818B2/en
Application filed by MDS Inc filed Critical MDS Inc
Publication of EP1958233A1 publication Critical patent/EP1958233A1/fr
Publication of EP1958233A4 publication Critical patent/EP1958233A4/fr
Application granted granted Critical
Publication of EP1958233B1 publication Critical patent/EP1958233B1/fr
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/02—Details
    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/0027—Methods for using particle spectrometers
    • H01J49/0031—Step by step routines describing the use of the apparatus

Definitions

  • the invention relates to mass analyzers.
  • chromatographic devices such as liquid chromatographic (LC) columns used in combination with mass spectrometers, as for example in combination hquid-chromatography - recursive mass spectroscopy (LC-MS/MS) mass analyzers.
  • LC-MS/MS combination hquid-chromatography - recursive mass spectroscopy
  • a chromatographic device causes the analyte matrix to be released or otherwise provided to the mass spectrometer in a distributed manner, such that va ⁇ ous analytes are provided to the mass spectrometer over va ⁇ ous periods of time.
  • MRM multiple reaction monitoring
  • other recursive or dist ⁇ aded-analysis techniques can be employed to analyze the analytes as they are received by the mass spectrometer.
  • MRM techniques involve multiple scannings by the mass spectrometer.
  • the multiple scannings are adapted, as for example by configuring the mass spectrometer to provide suitable electromagnetic fields, for the detection of ions of varying mass-charge (m/z) ratios as they are released by the chromatographic device over time.
  • m/z ratios mass-charge ratios to be analyzed
  • the invention provides improved systems, apparatus, methods, and programming useful for the automated analysis of compounds, and particularly of complex substance matrices, using mass spectrometers.
  • Systems, apparatus, methods, and programming according to the invention provide for the automatic determination by a controller of a mass spectrometer of an analysis operation to be implemented using the mass spectrometer, the analysis operation adapted specifically for analysis of one or more substances based contained within a compound based on identification of the compound and/or substances provided by a user of the spectrometer, and a database or other library of information concerning suitable processes or process steps for analyzing substances.
  • a user is enabled to provide an identifier, such as a name or other unique means of specification, to the controller, for use by the controller m accessing a data base or other information library and automatically determining an optimal duty cycle for each of a plurality of analytes contained in a compound comprising a plurality of substances, and determining command signals suitable for configuring the mass analyzer to implement such duty cycles.
  • the duty cycles may be implemented, for example, on a recursive mass analyzer such as a Multiple Reaction Monitoring (MRM) or Enhanced Product Ion (EPI) mass spectrometer.
  • MRM Multiple Reaction Monitoring
  • EPI Enhanced Product Ion
  • Figures 1 and 2 are schematic diagrams of mass analyzers suitable for use m implementing the invention.
  • Figure 3 is a schematic diagram of a controller suitable for use m implementing the invention.
  • Figure 4 is a schematic diagram of a process suitable for use in implementing the invention.
  • FIGS 1 and 2 are schematic diagrams of mass analyzers suitable for use in implementing the invention.
  • Mass analyzer(s) 100 comprise ion or compound source(s) (hereinafter "ion source(s)" or “IS(s)”) 12, mass spectrometer (s) ("MS(s)”) 14, and controller(s) 54.
  • ion source(s) or “IS(s)"
  • MS(s) mass spectrometer
  • controller(s) 54 controller(s) 54.
  • the example shown in Figure 1 is more general than that shown in Figure 2, and illustrates the concept that any combination of an ion source(s), mass spectrometer(s), and controller of any type(s) adaptable for the purposes disclosed herein may be used in implementing the invention; and illustrates general conceptual relationships of the components of mass analyzer 100 to each other.
  • ion source 12 provides analyte ions to mass spectrometer 14 for analysis, while controller 54 controls the operation of mass spectrometer 14 and optionally ion source 12.
  • the term ion source can apply generally to each and/or all of the various components of the sample introduction system, including, for example, those used in liquid sample handling, liquid chromatography and the ionizing systems described below.
  • the ionization (ionizer) part of the ion source 12, in which ions are generated can be a separate component associated with the mass spectrometer 14 or there can be a mass spectrometer interface where the ions are generated by ionization methods generally known in the art.
  • mass analyzer 100 comprises a liquid chromatography - recursive mass spectrometry (LC -MS/MS) mass analyzer 110.
  • LC-MS/MS mass analyzer 1 10 comprises an ion source 12 m the form of liquid chromatograph 212 and ionizer 218 (ionspray as shown) for generating ions, and mass spectrometer 14 comprising triple quadrupole mass spectrometer 214.
  • liquid chromatography is an analytical chromatographic technique used to separate ions dissolved in solvent(s), and is one way in which, for example, multiple substances within a given compound can be introduced to the MS interface to be ionized, and thus ions of varying m/z ratios provided to a mass spectrometer over a period of time, in a distributed manner.
  • analytes of interest When for example a sample solution comprising the targeted analytes is introduced via sample injector 213 to solvent 215 provided by pump 216 and placed in contact with suitable second solid or liquid phase reaction agent(s) in column 217, reactions may be caused which have the effect of separating analytes of interest from other substances
  • analytes of interest which typically comprise ions of varying m/z ratios, may be introduced to a mass spectrometer 14, 214 in a distributed manner over a range of times.
  • ion sources including the ionizers 218, such as an ionspray, and LC columns are suitable for use in implementing the invention described herein.
  • Preferred ion sources are those which separate analytes within the test matrix in such a way that the analytes or analyte ions are provided to the mass spectrometer 14 in a distributed manner, i e., over a range of times, so as to facilitate recursive mass analyses by mass spectrometer 14 using MRM or other suitable techniques.
  • LC columns represent only one type of source for introducing analyte solution to be ionized that is currently available and suitable for use in implementing the invention.
  • Analytes may be introduced to the mass spectrometer 14 by means other than LC; for example, analytes may be separated based on a variety of selective extraction or de ⁇ vatization techniques, and presented in solution form to the mass spectrometer 14 without the benefit of further LC separation.
  • analytes are crystallized with or without a matrix and introduced to the mass spectrometer 14 for ionization as is the case with mat ⁇ x-assisted-laser-desorption-ionization (MALDI), or other surface ionization applications.
  • MALDI mat ⁇ x-assisted-laser-desorption-ionization
  • Mass spectrometer 14 in Figure 2 comprises a triple quad mass spectrometer device
  • collimatmg quadrupole QO can for example be located m a chamber 16 maintained at a pressure around 10.sup.-2 torr.
  • collimating rod set 22 Upstream from rod set Ql within chamber 18, m the embodiment shown, is a short collimating rod set 22. Collimating rod set 22 can for example be used to focus ions of selected m/z ratios prior to their being introduced to rod set Ql .
  • Mass spectrometer 214 can further comprise downstream chamber 18, comprising t ⁇ ple rod sets Ql, Q2 and Q3, with Q2 being indicated withm an interior subsidiary chamber 20.
  • Chamber 18 can be maintained at a pressure of approximately 10.sup.-5 torr, while the subsidiary chamber 20 is supplied with nitrogen or argon gas as indicated at 21 for effecting collision-induced dissociation (CID).
  • CID collision-induced dissociation
  • chamber 20 is typically maintained at a pressure of around 10. sup. -2 torr.
  • the various chambers 16, 18, 20 can be connected in known manner to suitable pumps, as indicated at 21, 24, 25 and 26.
  • differentially-pumped region 12 can be connected to a roughing pump, which can serve to back up higher performance pumps connected to the pump connections 25 and 26.
  • Rod sets Ql and Q3 can be operated in va ⁇ ous modes, including a mass-resolving mode, to select ions of particular m/z ratios. Selected ions pass through into Q2 and may be subjected to CID and/or other desired reaction. The resulting product ions and any remaining precursor ions may then be passed through into mass-resolvmg rod set Q3 and recorded by detector 28.
  • ions provided by ion source 12, 212 can be controlled by the va ⁇ ous components of tandem quadrupole ion guide 250 in order to provide the ions to mass resolver Q3 in desired sequences.
  • ions of various m/z ratios can be provided to Q3 at desired times and in desired sequences by suitably controlling gas pressures in the va ⁇ ous chambers or devices 16, 18, 20, 220, 240, and/or by suitably controlling voltages applied across the electrodes of rod sets QO, Ql, Q2, Q3 and 22.
  • control signals suitable for controlling such gas pressures and voltages can be provided by controller 54.
  • mass spectrometers of any configurations or capabilities compatible with the purposes desc ⁇ bed herein are suitable for use m implementing the invention.
  • QTrap quadrupole linear ion trap
  • QqTOF tandem quadrupole time-of- flight
  • mass spectrometers which may be developed in the future, are suitable for use in implementing the invention.
  • MRM Multiple Reaction Monitoring
  • EPI Enhanced Product Ion
  • Mass analyzer 100, 110 further comp ⁇ ses controller 54, which is adapted for receiving, storing, and otherwise processing data signals acquired from or otherwise provided by user- controlled input device(s) and/or by mass analyzer 100, 110; and for executing suitable algorithms to determine, and for providing command signals adapted for the control of operations performed by mass analyzer 100, 110 in accordance with such signals.
  • controller 54 is adapted for interpreting and providing signals useful for controlling voltages and pressures applied by and maintained within mass spectrometer 14, 214, and optionally for controlling ion source 12, 212.
  • Controller 54 further provides a user interface suitable for controlling the mass analyzer 100, 110, and its components, and thus can include input/output devices suitable for accepting from the user and implementing commands suitable for analyzing substances.
  • controller 54 is adapted for receiving, from an input source 62, signals representing ⁇ dentifier(s) identifying one or more substances, using the ⁇ dentifier(s) to automatically access a data set comprising analysis parameters associated with the identifier, and, using the accessed data, automatically determining and providing to the mass spectrometer 14, 214 a set of command signals for use by a mass spectrometer in analyzing the substance(s).
  • Controller 54 may further be adapted for processing data acquired by mass spectrometer 14, 214 m response to the provided command signals, and for using such acquired data in determining command signals for use by the mass spectrometer in further analyzing the substance(s).
  • controller 54 can be adapted to store data acquired from mass spectrometer 14, 214 representing substances identified by mass analyzer 100, and/or to process such data for output to a user in human-interpretable form such as a printed or displayed graph or plot.
  • controller 54 can comprise any data-acquisition and processing system(s) or device(s) suitable for use in accomplishing the purposes described herein.
  • Controller 54 can comprise, for example, a suitably-programmed or - programmable general- or special -purpose computer or computer chip, or other automatic data processing equipment, with associated programming and data acquisition, input, output,
  • controller 54 preferably comprises or is linked to or otherwise associated with suitable volatile and/or persistent memory(s).
  • controller 54 can comprise one or more automatic data processing chips adapted for automatic and/or interactive control by approp ⁇ ately-coded structured programming, including one or more application and operating system programs, and any necessary or desirable volatile or persistent storage media.
  • processors, programming languages, data acquisition, and control devices suitable for implementing the invention are now available commercially, and will doubtless hereafter be developed.
  • controllers comprising suitable processors, memories, input and output devices, and programming are those incorporated in the API 3000TM or API 4000TM LC- MS/MS systems available through MDS Sciex of Ontario, Canada.
  • an automated mass analyzer is any mass analysis device adapted to perform one or more operations useful in or required for mass analysis of target substances without a requirement for specific user command inputs.
  • Combinations of controllers 54 adapted for such purposes with mass analyzers 100, 110 are examples of automated mass analyzers.
  • controller 54 comprises one or more processors 56 and associated volatile memory 58, persistent memory 60, input device(s) 62, and output device(s) 64.
  • Controller 54 is communicatively linked to mass spectrometer 12, 214 and to ion source 12, 212 (including various individual components thereof), in order to obtain data signals there from and to provide command signals thereto, as described herein.
  • Controller 54 may further be communicatively linked to one or more remote data bases 66 via a communications network 76 such as a wired or wireless public or private network, such as the Internet or a local or wide-area network.
  • a communications network 76 such as a wired or wireless public or private network, such as the Internet or a local or wide-area network.
  • memories 58, 60, input and output devices 62, 62, and communications interface 66 can comprise any suitable devices or components, including for example optical and magnetic ROMs and RAMs, keyboards, pointing devices, display screens, p ⁇ nters, wireless devices, and modems.
  • suitable devices and components are now commercially available, and will doubtless hereafter be developed
  • FIG. 4 is a schematic diagram of a process suitable for use in implementing the invention.
  • Process 400 illustrated in Figure 4 is suitable for implementation using, for example, mass analysers 100, 110 such as those shown in Figures 1 and 2, under the control of controllers as shown in Figure 3, executing programs implementing suitably-programmed algorithms; and is desc ⁇ bed below as if so implemented. It is to be understood, however, that, as desc ⁇ bed herein, process illustrated 400 in Figure 4 can be implemented using a wide variety of system and component configurations, including a wide variety of programming techniques.
  • controller 54 acquires or otherwise receives from an input source signals representing ⁇ dentif ⁇ er(s) identifying one or more compounds or substances to be analysed.
  • a user of a mass analyzer 100, 110 uses a suitably-programmed and/or controlled input device 62 such as a keyboard, pointing device, and / or interactive screen display to enter data representing an accepted compound or substance name, or abbreviation thereof, or other unique identifier.
  • the input device provides signals representing the entered data to the processor(s) 56.
  • the user can enter data identifying one or more chemicals, biological products such as a clinical test or forensic samples, or nutritional substances such as a foods or beverages by name, or by other coded reference such as index or reference number(s).
  • the user may also enter additional data identifying or otherwise specifying information relating to the manner in which the identified substance(s) are to be made available to the mass spectrometer 14 for analysis.
  • additional data identifying or otherwise specifying information relating to the manner in which the identified substance(s) are to be made available to the mass spectrometer 14 for analysis.
  • a mass analyzer 100 comprises an LC column 212
  • the user can input data representing such time and/or time range, or coded reference to such information.
  • additional data can be used, for example, to further improve the efficiency of the analysis of the identified substance(s).
  • Signals representing any such data input by the user may be provided to processor(s) 56 for use in controlling analysis of the identified substance(s) by the mass analyser 100.
  • the efficiency of the mass analyser 100 may be improved by monitoring only for those compounds which are expected to pass from the LC column at specific times during the analysis. For example, m the analysis of apple products for pesticide residues, there may be 400 compounds to be monitored. Each compound has a specific elution time from the LC column.
  • the user may simply provide information about the compounds to be analysed such as their mass, desired parent-daughter ion transitions to be monitored, and elution time or time window, and the system can automatically control the analyser scan functions during the analysis such that only the compounds expected at each time point du ⁇ ng the analysis would be scanned for, thus at any given time du ⁇ ng the analysis much fewer than the total 400 compounds are being scanned for. Because the system can interpret the information provided by the user on a scan-by-scan basis, there is no need to construct a complicated acquisition method to the mass analyser 100 m advance of the analysis.
  • controller 54 using the ⁇ dentifier(s) received at 402, automatically accesses data comprising analysis parameters associated with the ⁇ dentifier(s).
  • processor(s) 56 can, by causing the transmission of suitable command signals, without further input from the user beyond the identifiers received at 402, query one or more of memories / databases or other data stores 58, 60, 66 to retrieve data associated with a compound associated with identifiers received at a process step 402, the compound comprising a plurality of substances and times or ranges of times over which those substances can be expected to be released or otherwise made available to a mass spectrometer 14 by an ionizer 218 as provided by the output from an LC column 214.
  • the ionizer 218 can generate ions directly from the output of the LC column in real time or the output substance from the LC column can be deposited onto a MALDI plate surface for future ionization as known in the art
  • complex compounds comprising multiple known substances suspended or dissolved in known solvents have been analyzed using LC columns comprising known reaction agents, and the output of substances from the LC columns recorded as a function of time.
  • data sets comprising identifiers such as names representing compounds, and/or substances, and the times and/or ranges of times (including suitable tolerances for variations) at which various ions are released from the LC column (sometimes known as "retention time" are known and can be used in accordance with the invention.
  • An example of an application of this aspect of the invention is an on-demand analysis application for rapid drug screening.
  • this invention provides the user with the ability to simply supply a list of desired analytes.
  • the system can then automatically perform the appropriate mass analyser 100 functions to detect the compounds by obtaining information about scanning parameters, elution times, desired identification ions, etc from a database.
  • controller 54 using data accessed at 404, provides command signals determined at 406 to mass analyzer 100, in order to configure the mass analyzer for analysis of substance(s) provided by ion source 14.
  • command signals thus provided cause mass analyzer to be configured accordingly, and are thus used by mass analyzer 100 in performing a desired analysis of the substance(s) and as desired in any subsequent processing of data obtained by the mass analyzer 100
  • One of the advantages offered by the invention is improved analysis of multiple compounds and/or the analysis of relatively complex compounds.
  • the invention can be useful, for example, in enabling controller 54 to cause the re-configuration of mass analyzer 100 and/or any components thereof in performing sequential analyses of multiple substances, or in breaking down the analysis of complex compounds into multiple steps, and re-configurmg one or more components of mass analyzer 100 for efficient analysis during such analyses or steps, as for example m LC/MS/MS or other recursive spectroscopy.
  • the system may combine this data with the data collected by the mass analyzer 100 on a per scan basis to correct for deviations in LC performance which may result in compounds of interest elutmg at times different from those specified, and/or to adjust the mass analyser 100 duty cycle to improve the signal-to-noise ratio for low intensity peaks, and/or any other appropriate adjustment of the mass analyser 100 parameters which my be indicated by the current or previous scan data.
  • a determination is made by controller 54 as to whether any subsequent analyses, analysis steps, or mass analyser 100 adjustments are to be performed. If so, process 402 - 408 is repeated as desired.
  • the invention provides, for example, for increased performance in the execution of multiple scan duty cycles in LC/MS/MS or other recursive analyses.
  • a recursive mass analyzer such as an LC-MS/MS device 110 can be configured to perform a se ⁇ es of scanning by for example configuring the device to provide suitable electromagnetic fields m devices QO, Ql, Q2, Q3, and 22 of Figure 2, and/or suitable pressures m chambers or devices 16, 18, 20, 220, 240, at varying points in time, for the optimal detection of ions of varying mass-charge (m/z) ratios as they are released by a chromatographic device.
  • the mass analyzer may be configured for the detection of ions of varying m/z ratios du ⁇ ng the time periods at which they are released by the chromatographic device and made available to the mass analyzer.
  • the analytes appear individually for a limited time (peak width) in the LC stream, and because the detector must scan for hundreds of compounds individually in a looped sequence of MRM or other compound specific scan functions, the number of data points available to characterize the presence of a compound in the sample is limited by the number of complete scan cycles which can be accomplished within the typical peak width.
  • a scan cycle comprising the individual selective scans for 400 compounds may take up to 20 seconds, depending on the instrument.
  • typical peak widths of 10-30 seconds it would be normal to expect only one or two data points per peak. In extreme cases, there is the likelihood that a compound would go undetected as the peak width is smaller than the scan cycle and thus occurs between subsequent scans, thereby elutmg undetected.
  • the user can simply provide the system with a list of compound names and expected elution times or time windows.
  • the system would then automatically, on a scan-by-scan basis, determine which compounds to scan for, thus significantly reducing the number of compounds which are being simultaneously scanned for at any given time during the analysis.
  • the systems has the ability to adjust mass analyser 100 properties on a scan- by-scan basis to perform subsequent MS/MS analysis for compound confirmation, correct for variations in LC performance, and improve signal-to-noise ratios of small signals. This has the effect of increasing the number of data points which represent the elutmg analyte peaks, and increasing the instrument duty cycle with respect to each individual analyte.
  • the data generated by such a multi-compound screening method can be improved by reducing the probability of an undetected peak, improving the quality of peak area determination (quantitation) and allowing for an increase m the speed of analysis. Furthermore, the implementation of large numbers of analytes in a method becomes very simple for the user as all that is required is a list of expected elution times for the desired compounds which the system can interpret in order to approp ⁇ ately control the detector du ⁇ ng the analysis.
  • process 400 illustrated in Figure 4 and other processes described herein are suitable for implementation using mass analysers such as those shown in Figures 1 and 3, and controllers as shown in Figure 3, executing suitably-programmed algorithms.
  • algorithms can be coded or otherwise programmed in a wide variety of ways to provide computer-readable and -executable program codes, including for example through the use of binary language or high-level computer languages such as C++, FORTRAN, C# or any other suitable programming language.
  • the implementation of the code may be approached m several different ways, and the code and information storage necessary may be implemented on either the instrument controller of the host computer.

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  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)

Abstract

L'invention porte sur des systèmes, appareils, procédés, et programmes d'analyse automatique de composés complexes au moyen de spectromètres de masse. Lesdits systèmes, appareils, procédés, et programmes permettent la détermination automatique par le contrôleur (54) d'un spectromètre de masse (14, 214) d'une opération d'analyse à effectuer par le spectromètre de masse. Ladite opération d'analyse est spécialement adaptée à l'analyse d'une ou de substances contenues dans un composé, sur la base de l'identification du composé et/ou de substances fournies par l'utilisateur du spectromètre, et d'une base de données (66) ou d'autres bibliothèques d'informations, concernant des processus ou des étapes de procédés convenants d'analyse de substances.
EP06828156.7A 2005-12-07 2006-12-07 Analyse automatique de matrices complexes au moyen d'un spectrometre de masse Active EP1958233B1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US74291005P 2005-12-07 2005-12-07
US11/567,281 US7548818B2 (en) 2005-12-07 2006-12-06 Automated analysis of complex matrices using mass spectrometer
PCT/CA2006/001999 WO2007065266A1 (fr) 2005-12-07 2006-12-07 Analyse automatique de matrices complexes au moyen d'un spectrometre de masse

Publications (3)

Publication Number Publication Date
EP1958233A1 true EP1958233A1 (fr) 2008-08-20
EP1958233A4 EP1958233A4 (fr) 2011-10-05
EP1958233B1 EP1958233B1 (fr) 2017-06-14

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EP06828156.7A Active EP1958233B1 (fr) 2005-12-07 2006-12-07 Analyse automatique de matrices complexes au moyen d'un spectrometre de masse

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EP (1) EP1958233B1 (fr)
JP (1) JP2009518631A (fr)
CA (1) CA2631218C (fr)
WO (1) WO2007065266A1 (fr)

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EP2263250B1 (fr) * 2008-03-20 2017-12-27 DH Technologies Development Pte. Ltd. Systèmes et procédés pour analyser des substances à l'aide d'un spectromètre de masse
GB0909285D0 (en) * 2009-05-29 2009-07-15 Micromass Ltd Method to detect and sequence post translationally modified peptides
DE202011111053U1 (de) 2010-10-29 2018-11-21 Thermo Fisher Scientific Oy Automatisiertes System zur Probenaufbereitung und -analyse
GB201104225D0 (en) * 2011-03-14 2011-04-27 Micromass Ltd Pre scan for mass to charge ratio range
JP5812881B2 (ja) * 2012-01-23 2015-11-17 株式会社日立ハイテクノロジーズ タンデム型質量分析装置及びその質量分析方法
JP6368067B2 (ja) 2012-04-23 2018-08-01 株式会社日立ハイテクノロジーズ 質量分析装置及び質量分析方法
JP6020395B2 (ja) * 2013-09-09 2016-11-02 株式会社島津製作所 クロマトグラフ質量分析を用いた薬物分析方法
JP6311387B2 (ja) * 2014-03-26 2018-04-18 株式会社島津製作所 化合物分析方法、化合物分析装置、及び化合物分析用プログラム

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Also Published As

Publication number Publication date
EP1958233A4 (fr) 2011-10-05
WO2007065266A1 (fr) 2007-06-14
CA2631218C (fr) 2014-12-02
CA2631218A1 (fr) 2007-06-14
EP1958233B1 (fr) 2017-06-14
JP2009518631A (ja) 2009-05-07

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