WO2016042627A1 - 質量分析装置 - Google Patents
質量分析装置 Download PDFInfo
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- WO2016042627A1 WO2016042627A1 PCT/JP2014/074591 JP2014074591W WO2016042627A1 WO 2016042627 A1 WO2016042627 A1 WO 2016042627A1 JP 2014074591 W JP2014074591 W JP 2014074591W WO 2016042627 A1 WO2016042627 A1 WO 2016042627A1
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
- H01J49/02—Details
- H01J49/10—Ion sources; Ion guns
- H01J49/16—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
- H01J49/165—Electrospray ionisation
- H01J49/167—Capillaries and nozzles specially adapted therefor
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- 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
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
- H01J49/26—Mass spectrometers or separator tubes
- H01J49/34—Dynamic spectrometers
- H01J49/42—Stability-of-path spectrometers, e.g. monopole, quadrupole, multipole, farvitrons
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
- H01J49/0095—Particular arrangements for generating, introducing or analyzing both positive and negative analyte ions
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- H—ELECTRICITY
- H01—ELECTRIC ELEMENTS
- H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
- H01J49/00—Particle spectrometers or separator tubes
- H01J49/02—Details
- H01J49/10—Ion sources; Ion guns
- H01J49/16—Ion sources; Ion guns using surface ionisation, e.g. field-, thermionic- or photo-emission
- H01J49/165—Electrospray ionisation
Definitions
- the present invention relates to a mass spectrometer, and more particularly, to a mass spectrometer equipped with a high-voltage power supply device capable of switching polarity for applying, for example, a high voltage having a polarity corresponding to the polarity of an ion to be analyzed to an ion source or the like.
- LC-MS liquid chromatograph mass spectrometer
- An ion source using an atmospheric pressure ionization method such as an ESI method or an atmospheric pressure chemical ionization (APCI) method is used.
- ESI ion source it is necessary to apply a high voltage (for example, about ⁇ several [kV]) having the same polarity as ions to be analyzed to the tip of a nozzle that sprays a liquid sample.
- a high voltage power supply device having a configuration in which the polarity can be switched is used.
- a device described in Patent Document 1 is known.
- This high-voltage power supply device includes a positive voltage generation circuit and a negative voltage generation circuit each including a DC-DC conversion circuit using an insulating transformer, and includes a positive output terminal by the positive voltage generation circuit and a negative electrode by the negative voltage generation circuit.
- a resistor is connected in parallel to the output terminal on the side, and the two resistors are connected in series. Then, one end of the resistors connected in series is used as a reference side, and a positive or negative high voltage is extracted from the other end.
- a predetermined drive signal is supplied from the control circuit to the switching elements included in the positive voltage generation circuit and the negative voltage generation circuit, respectively, so that a high voltage is generated in the positive voltage generation circuit and the negative voltage generation circuit.
- one output voltage of the positive voltage generation circuit and the negative voltage generation circuit changes from the positive high voltage + HV to zero, and at the same time the other output Control is performed so that the voltage changes from zero, overshoots, and converges to a negative high voltage -HV. In this way, the time required for polarity switching between positive and negative is shortened by intentionally overshooting the voltage on the side to be raised.
- An apparatus described in Patent Document 2 is known as a high-voltage power supply apparatus that further speeds up the polarity switching between positive and negative.
- resistors connected in parallel to the positive-side output terminal of the positive voltage generation circuit and the negative-side output terminal of the negative voltage generation circuit in the device described in Patent Document 1 for example, FET It is replaced with a switch circuit.
- a circuit in which two resistors are connected in series is connected in parallel with each switch circuit, and a signal extracted from the connection point of the two resistors on the positive electrode side is turned on / off of the switch circuit on the negative electrode side.
- a signal taken out from the connection point of the two negative-side resistors is inputted as an on / off drive control signal for the positive-side switch circuit.
- this high voltage power supply device for example, when the positive voltage generating circuit is operated, a positive high voltage + HV appears at the output terminal, and the negative voltage generating circuit is substantially stopped so that the voltage at the output terminal is almost equal. Suppose that it is zero. At this time, a voltage obtained by dividing the high voltage + HV by the ratio of the resistance values of the resistors is generated at the connection point of the two resistors on the positive output side, and is given to the switch circuit on the negative electrode side. As a result, the switch circuit is turned on, and a conductive state is established between the output terminals of the negative voltage generating circuit. When the polarity of the voltage is switched from positive to negative from this state, the positive voltage generation circuit is stopped and the negative voltage generation circuit operates.
- the negative-side switch circuit When the voltage at the output terminal of the positive voltage generation circuit drops to a predetermined voltage, the negative-side switch circuit is turned off. On the other hand, as the voltage at the output terminal of the negative voltage generation circuit increases, the positive-side switch circuit is turned on. As a result, the electric charge remaining at the output terminal of the positive voltage generation circuit is rapidly discharged through the switch circuit, and the output voltage of the positive voltage generation circuit is quickly reduced to zero.
- the positive and negative switch circuits provided at the output end forcibly release the charge remaining at the output end of the polarity side that is going to change to zero when switching between positive and negative polarities. To work. Thereby, the fall of the voltage which is going to change to zero becomes quick, and the polarity switching between positive and negative becomes faster.
- LC / MS analysis can be performed while alternately switching between the positive ion measurement mode and the negative ion measurement mode in a short time. This makes it possible to detect both a compound that tends to be a positive ion and a compound that tends to be a negative ion without omission, and is particularly useful for simultaneous multi-component analysis.
- the applied voltage to the ESI ion source is adjusted for each ion to be measured by SIM (selective ion monitoring) or MRM transition (combination of precursor ions and product ions) to be measured by MRM (multiple ion monitoring).
- SIM selective ion monitoring
- MRM transition combination of precursor ions and product ions
- a capacitor is generally connected to the output end in order to smooth the output voltage.
- the capacitor can be charged quickly by increasing the output current, so that the voltage rises at a high speed.
- the voltage value absolute voltage value
- the voltage value absolute voltage value
- the cycle of performing MRM measurement for ions derived from a plurality of target compounds one after another is repeated, but if switching of the applied voltage takes time as described above, It may be necessary to shorten the acquisition time (so-called dwell time) or limit the number of MRM transitions to be measured simultaneously. In the former case, detection sensitivity is sacrificed. In the latter case, the number of compounds that can be measured at one time is reduced. In some cases, multiple measurements on the same sample may be required. obtain.
- the present invention has been made to solve the above-described problems, and the object of the present invention is, for example, a settling time for stabilizing the voltage when MRM measurement is repeatedly performed for a plurality of MRM transitions.
- An object of the present invention is to provide a mass spectrometer capable of performing efficient analysis by shortening unnecessary time as much as possible, shortening the time required for one cycle, or lengthening the dwell time for one MRM transition. .
- the present invention provides an ion source that ionizes a compound in a sample, a mass separation unit that separates ions derived from the compound according to a mass-to-charge ratio, and a separation according to the mass-to-charge ratio.
- a mass separation unit that separates ions derived from the compound according to a mass-to-charge ratio
- a separation according to the mass-to-charge ratio A plurality of selected ion monitoring (SIM) measurements in which ions to be measured are different, or a plurality of MRM transitions that are combinations of precursor ions to be measured and product ions.
- SIM selected ion monitoring
- a mass spectrometer that repeatedly executes a cycle for performing multiple reaction monitoring (MRM) measurement of a) an information collecting unit that collects information on a plurality of SIM measurement target ions or a plurality of MRM measurement target MRM transitions executed in one cycle within an arbitrary measurement time range; b) a measurement order determining unit that determines the order in which SIM measurement for different ions in one cycle or MRM measurement for different MRM transitions is performed, and a plurality of SIM measurement targets in one cycle collected by the information collecting unit Measurements for ions or a plurality of MRM transitions are aggregated for each polarity of the voltage applied to the ion source suitable for each of the SIM measurement target ions or MRM transitions, and then according to the absolute value of the applied voltage within the same polarity.
- a measurement order determination unit that determines the measurement order in one cycle by rearranging the measurement order; It is characterized by having.
- the mass spectrometer according to the present invention may further include a control unit that controls each unit so as to perform SIM measurement or MRM measurement according to the measurement order determined by the measurement order determination unit.
- the mass spectrometer according to the present invention typically has a quadrupole mass spectrometer equipped with one quadrupole mass filter as a mass separator, or a quadrupole before and after the collision cell, respectively.
- This is a tandem quadrupole mass spectrometer equipped with a mass filter.
- the ion source is typically an ion source based on an electrospray ionization (ESI) method including a nozzle that charges a sample solution and sprays it into the air atmosphere.
- ESI electrospray ionization
- the applied voltage is a voltage applied to the nozzle of the ESI ion source.
- the mass spectrometer according to the present invention is a tandem quadrupole mass spectrometer, and a sample through a liquid chromatograph column is introduced into the tandem quadrupole mass spectrometer, Assume that a quantitative analysis is performed on one or more known target compounds contained in a sample.
- the MRM transition corresponding to the target compound that is, the set of the mass-to-charge ratio of the precursor ion and the mass-to-charge ratio of the product ion is known. Therefore, the analyst designates the timing at which the target compound elutes from the column outlet, that is, the measurement time range corresponding to the retention time, and the MRM transition corresponding to the compound. Often multiple MRM transitions are specified for a single compound. In the case of multi-component simultaneous analysis, since the measurement time ranges for a plurality of compounds overlap, even if one MRM transition is designated for one compound, MRM measurement for a plurality of MRM transitions is executed in a certain cycle. Needs may arise. Therefore, the information collection unit collects information on a plurality of MRM measurement target MRM transitions executed during one cycle within an arbitrary measurement time range. Multiple MRM transitions performed during one cycle may be from the same compound or may be from different compounds.
- the information collection unit may include an information designating unit in which an analyzer designates a plurality of SIM measurement target ions or a plurality of MRM measurement target MRM transitions to be executed in one cycle.
- an analyzer designates a plurality of SIM measurement target ions or a plurality of MRM measurement target MRM transitions to be executed in one cycle.
- a plurality of MRM transitions designated by the analyst via the information designation unit become MRM transitions to be executed in one cycle as they are.
- the measurement order determination unit obtains a suitable applied voltage for each of a plurality of MRM transitions to be executed in one cycle, first collects the MRM transitions for each polarity of the applied voltage, and then applies the applied voltage within the same polarity. Rearrange the order of measurement according to the absolute value of. That is, the MRM transition in which the applied voltage is positive and the MRM transition in which the applied voltage is negative are separated, and the order is rearranged according to the absolute value of the applied voltage among the plurality of MRM transitions in which the applied voltage is positive. The order is rearranged according to the absolute value of the applied voltage among the plurality of MRM transitions that are negative.
- Information relating to the applied voltage suitable for each MRM transition may be input by the analyst together with the information specifying unit when the MRM transition is specified by the information specifying unit or the like.
- a suitable applied voltage for a specified MRM transition may be derived using prior information such as a table in which the correspondence relationship between MRM transitions and suitable applied voltages in various compounds is stored in advance.
- the optimum applied voltage to the ESI ion source depends not only on the type of compound but also on other conditions such as the type of LC mobile phase and the type of sample solvent.
- the measurement order determining unit may rearrange the measurement order so that the absolute value of the applied voltage increases from the lowest in the same polarity.
- the high-voltage power supply device disclosed in Patent Document 2 switching between positive and negative polarities is performed at high speed. Therefore, the applied voltages having positive polarities are arranged in descending order of absolute values and the voltage is maximized. Even if the polarity is switched to negative after that, the polarity is switched quickly.
- the applied voltages having negative polarity are arranged in order from the lowest absolute value and the polarity is switched to the positive after the voltage reaches the maximum, the polarity is switched quickly. Therefore, in the measurement order determined by the measurement order determination unit, the voltage switching operation in which the voltage switching takes time and the voltage drops is substantially eliminated, and the settling time for switching the voltage can be shortened.
- the mass spectrometer of the present invention when measurement is performed while changing the voltage applied to the ion source or the like stepwise within a predetermined measurement time range, the following is immediately performed after changing the voltage. Since the voltage is settled, the settling time when the voltage is not stable can be shortened. As a result, even if the cycle time, which is the period of one cycle, is the same as that of the conventional apparatus, the effective data acquisition time of SIM measurement or MRM measurement, that is, the dwell time becomes longer. Sensitivity can be increased. In addition, if the dwell time is the same as that of the conventional apparatus, the cycle time can be shortened by the amount that the settling time has been shortened.
- the sampling time interval is shortened, and one compound is eluted from the previous LC.
- the number of data points that can be obtained during a certain period can be increased.
- the peak top can be reliably grasped, the reproducibility of the shape of the peak skirt portion is improved, and the accuracy of the peak area is improved, so that the accuracy of quantification based on the peak area can be improved.
- the block diagram of the principal part of the tandem quadrupole-type mass spectrometer which is one Example of this invention.
- FIG. 1 is a configuration diagram of a main part of a tandem quadrupole mass spectrometer according to the present embodiment.
- the tandem quadrupole mass spectrometer of the present embodiment has a degree of vacuum stepwise between the ionization chamber 1 at approximately atmospheric pressure and the high-vacuum analysis chamber 4 evacuated by a high-performance vacuum pump (not shown).
- This is a configuration of a multistage differential evacuation system including the first and second intermediate vacuum chambers 2 and 3 that are enhanced.
- the ionization chamber 1 is provided with an ESI probe 5 constituting an ESI ion source to which a sample solution eluted from an LC column outlet (not shown) is continuously supplied.
- a high voltage is applied to the nozzle at the tip of the probe 5 from a high voltage power supply 20, and the sample solution that has reached the nozzle is sprayed into the ionization chamber 1 while being given an offset charge.
- the sprayed droplets of the sample solution are micronized while being broken by electrostatic force or the like, and in the process, ions derived from the compound in the sample are generated.
- the ions are converged by an ion guide 7 disposed in the first intermediate vacuum chamber 2 and sent to the second intermediate vacuum chamber 3 through a small hole formed at the top of the skimmer 8.
- the ions are further converged by an ion guide 9 disposed in the second intermediate vacuum chamber 3 and sent to the analysis chamber 4.
- a front-stage quadrupole mass filter 10 a collision cell 11 in which a multipole ion guide 12 is disposed, a rear-stage quadrupole mass filter 13, and an ion detector 14 are disposed.
- ions are first introduced into the front quadrupole mass filter 10, and only ions having a specific mass-to-charge ratio selectively pass through the front quadrupole mass filter 10 as precursor ions.
- Precursor ions are introduced into the collision cell 11 and come into contact with a collision-induced dissociation (CID) gas supplied from a gas supply source (not shown) into the collision cell 11 to cause dissociation to generate various product ions.
- CID collision-induced dissociation
- the generated product ions are introduced into the rear-stage quadrupole mass filter 13, and only product ions having a specific mass-to-charge ratio selectively pass through the rear-stage quadrupole mass filter 13 and reach the ion detector 14.
- the ion detector 14 outputs an ion intensity signal corresponding to the number of incident ions to the data processing unit 21 as a detection signal.
- the mass-to-charge ratio of ions that can pass through the front-stage quadrupole mass filter 10 and the rear-stage quadrupole mass filter 13 depends on the voltage applied to the rod electrodes that constitute the mass filters 10 and 13. Therefore, by appropriately setting the voltage applied to the rod electrode, product ions having a specific mass-to-charge ratio generated from a precursor ion having a specific mass-to-charge ratio derived from a predetermined compound at a certain point in time Can be obtained.
- the control unit 30 includes, as functional blocks, an analysis control unit 31, an analysis sequence determination unit 32 that determines an analysis sequence, and an analysis sequence storage unit 35 that stores the determined analysis sequence. According to the analysis sequence stored in the storage unit 35, the above-described analysis can be performed by controlling the high-voltage power supply 20 that applies a voltage to the nozzles of the ESI probe 5 over time and other power supplies (not shown). Carry out.
- the analysis sequence determination unit 32 includes an analysis condition setting processing unit 33 and a measurement order rearrangement unit 34 as characteristic function blocks.
- the control unit 30 is connected to an input unit 36 that is a pointing device such as a keyboard and a mouse operated by the analyst, and a display unit 37 for displaying information and analysis results input and set by the analyst. .
- control unit 30 and the data processing unit 21 are performed by executing a dedicated control / processing software installed in advance on the computer using a general-purpose personal computer as a hardware resource. Can be realized.
- the high-voltage power supply 20 is a high-voltage power supply device capable of switching the positive / negative polarity of the output voltage at high speed as disclosed in Patent Document 2, for example.
- the high voltage power supply 20 when the polarity of the output voltage is switched from positive to negative, the charge remaining at the output terminal on the positive electrode side is forcibly released, and conversely, the polarity of the output voltage is switched from negative to positive. Sometimes the charge remaining at the output terminal on the negative electrode side is forcibly released. Accordingly, there is an advantage that the polarity switching between positive and negative can be performed more quickly than in the past.
- the MRM measurement for the MRM transition corresponding to the target compound is executed within the measurement time range in which the target compound elutes, that is, within the measurement time range of a predetermined time width near the retention time of the target compound. Then, a mass chromatogram (extracted ion chromatogram) is created for each MRM transition from the ion intensity signal obtained by MRM measurement. Then, a peak corresponding to the target compound is detected on the mass chromatogram, the peak area is calculated, and a quantitative value is obtained from the peak area value.
- the measurement time ranges corresponding to a plurality of target compounds overlap, and in the overlapped time range, it is necessary to sequentially perform MRM measurements for MRM transitions corresponding to the plurality of target compounds.
- the analyst designates the measurement time range determined in the vicinity of the retention time of the target compound and the MRM transition to be measured within the measurement time range.
- the analysis condition setting processing unit 33 displays a measurement time range, a compound name to be measured in the measurement time range, and the compound on the display unit 37.
- An input screen for prompting input of MRM transition (precursor ion m / z value, product ion m / z value), ion polarity and the like is displayed.
- the analyst makes a predetermined input on the input screen by the input unit 36.
- the input information is received by the analysis condition setting processing unit 33.
- the number of MRM transitions for one compound is not necessarily one, and there may be a plurality.
- the measurement order rearranging unit 34 determines the order of a plurality of MRM measurements to be executed in one cycle as follows.
- the order of measurement at this time is, for example, the order set by the analyst.
- the voltage applied to the nozzle for obtaining the best ionization efficiency in the ESI ion source differs depending on the type of compound or the MRM transition of the same compound. Therefore, the measurement order rearranging unit 34 collects information on the nozzle voltage that is optimal for the set compound and MRM transition. As described above, the nozzle voltage can be input by the analyst at the same time when the analyst sets the MRM transition for the target compound.
- a table indicating the relationship between a large number of compounds and MRM transitions and the optimum nozzle voltage is created and stored in advance, and the target compound designated by the analyst is stored.
- the optimum nozzle voltage corresponding to the MRM transition may be read out by referring to the table or the like.
- the optimum nozzle voltages are +2, +4, +3, +1, and +4 [kV] for the MRM transitions corresponding to the five types of compounds A, B, C, D, and E, respectively. I want.
- the analysis sequence is determined so that the MRM measurement is executed in the order shown in FIG.
- the analysis is performed by the analysis control unit 31 controlling each unit in accordance with the analysis sequence thus determined, the voltage applied to the nozzle of the ESI probe 5 from the high voltage power supply 20 in one cycle is shown in FIG. ). That is, as described above, a long settling time is required when the voltage changes in the same polarity in the direction in which the voltage drops. Therefore, for example, after performing MRM measurement for the MRM transition derived from compound B, It takes time to start the MRM measurement for the MRM transition. For this reason, the ratio of the period during which data can be collected effectively in the cycle time is not very large.
- the measurement order rearrangement unit 34 aggregates the ions having the same polarity of the target of MRM measurement to be performed in one cycle.
- the measurement order is rearranged, that is, sorted so that the absolute value of the applied voltage is increased in ascending order.
- the polarities are all positive and the same polarities are already gathered, so the measurement order is arranged so that the absolute value of the applied voltage increases in ascending order.
- the rearrangement is performed so that the nozzle voltage becomes + 1 ⁇ + 2 ⁇ + 3 ⁇ + 4 [kV].
- FIG. 2A shows an example in which the polarities of all the ions to be measured are positive
- FIG. 2B shows an example in which all the polarities of the ions to be measured are negative. Since the order of measurement is rearranged so that the absolute value of the applied voltage increases from the smallest value, in this example, the nozzle voltage is set to ⁇ 1 ⁇ ⁇ 2 ⁇ ⁇ 2.5 ⁇ ⁇ 3 [kV]. Rearrangement has been done.
- the analysis control unit 31 performs the analysis while controlling each unit according to the analysis sequence stored in the analysis sequence storage unit 35. Therefore, in one cycle corresponding to the example shown in FIG. 2 (a2), the voltage applied from the high voltage power supply 20 to the nozzle of the ESI probe 5 changes as shown in FIG. 3 (b). In this case, the settling time becomes longer because the voltage drops with the same polarity between the end point of one cycle and the start point of the next cycle, but otherwise the settling time increases. Is very short. Therefore, the cycle time is shortened as compared with the conventional apparatus shown in FIG.
- FIGS. 2 and 3 are examples in which the polarities of target ions of MRM measurement executed during one cycle are the same polarity, while FIGS. 4 and 5 show the polarities of target ions of MRM measurement executed during one cycle.
- This is an example of when both positive and negative are mixed.
- the rearrangement is performed so that the absolute value of the applied voltage increases in order from the smallest, so as shown in FIG. Rearrangement is performed so that the voltage is + 2 ⁇ + 3 ⁇ + 4 [kV], and in the negative polarity, rearrangement is performed so that the nozzle voltage is ⁇ 1.5 ⁇ ⁇ 2 ⁇ ⁇ 3 [kV].
- the order of a plurality of MRM measurements performed in parallel is rearranged according to the value of the voltage applied to the ESI ion source,
- Useless settling time can be shortened.
- the cycle time can be shortened to increase the number of data points, or instead of shortening the cycle time, the dwell time can be lengthened to improve the ion detection sensitivity.
- the present invention can be applied to a single type quadrupole mass spectrometer.
- the measurement may be rearranged as described above when performing a plurality of SIM measurements in one cycle.
- the present invention is not limited to an ESI ion source, and other ionization methods that require application of a high voltage with a polarity corresponding to the polarity of the ions during ionization, such as the DESI method and the PESI method. It is also applicable to a mass spectrometer equipped with
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Abstract
Description
a)任意の測定時間範囲内の1サイクル中に実行される複数のSIM測定対象のイオン又は複数のMRM測定対象のMRMトランジションについての情報を収集する情報収集部と、
b)1サイクル中で異なるイオンに対するSIM測定又は異なるMRMトランジションに対するMRM測定を実行する順序を決定する測定順序決定部であって、前記情報収集部により収集された1サイクル中の複数のSIM測定対象イオン又は複数のMRMトランジションに対する測定を、それらSIM測定対象イオン又はMRMトランジションにそれぞれ好適な前記イオン源への印加電圧の極性毎に集約したうえで、同じ極性の中で前記印加電圧の絶対値に従って測定の順序を並べ替えることで1サイクル中の測定順序を決定する測定順序決定部と、
を備えることを特徴としている。
なお、上述したように、ESIイオン源などへの最適な印加電圧は化合物の種類だけでなく、LCの移動相の種類、試料溶媒の種類など、他の条件にも依存するから、そうした条件も併せてできるだけ好適な印加電圧が求まるようにしておくことが望ましい。つまり、同じ化合物における同じMRMトランジションであっても、例えばLCの移動相の種類が異なった場合には、その移動相の種類に応じた、より好適な印加電圧が得られるようにしておくとよい。
特に特許文献2に開示されている高電圧電源装置の場合には、正負の極性の切替えは高速に行われるから、極性が正である印加電圧を絶対値の低いものから順に並べて該電圧が最大になったあとに極性を負に切り替えても、その極性の切替えは迅速に行われる。極性が負である印加電圧を絶対値の低いものから順に並べて該電圧が最大になったあとに極性を正に切り替える場合でも同様に、その極性の切替えは迅速に行われる。したがって、測定順序決定部により決定された測定順序では、電圧切替えに時間が掛かる、電圧が降下する方向の電圧切替え動作は実質的になくなり、電圧を切り替えるためのセトリングタイムを短くすることができる。
図1は本実施例のタンデム四重極型質量分析装置の要部の構成図である。
本実施例のタンデム四重極質量分析装置は、略大気圧であるイオン化室1と図示しない高性能の真空ポンプにより真空排気される高真空の分析室4との間に、段階的に真空度が高められた第1、第2中間真空室2、3を備えた多段差動排気系の構成である。イオン化室1には、図示しないLCのカラム出口から溶出する試料溶液が連続的に供給されるESIイオン源を構成するESI用プローブ5が設置されている。そのプローブ5先端のノズルには高電圧電源20から高電圧が印加され、ノズルに達した試料溶液は片寄った電荷を付与されつつイオン化室1内に噴霧される。噴霧された試料溶液の液滴は静電気力等により分裂しながら微細化され、その過程で試料中の化合物由来のイオンが生成される。
上記のような分析を実行するために、その分析実行に先立って、分析者は、目的化合物の保持時間付近に定めた測定時間範囲とその測定時間範囲内で測定すべきMRMトランジションを指定する。
具体的には、分析者が入力部36により所定の操作を行うと、分析条件設定処理部33は表示部37に、測定時間範囲、該測定時間範囲において測定する化合物名、該化合物に対応するMRMトランジション(プリカーサイオンm/z値、プロダクトイオンm/z値)、イオンの極性などの入力を促す入力画面を表示する。分析者は入力部36により、この入力画面上で所定の入力を行う。入力された情報は分析条件設定処理部33により受け付けられる。一つの化合物に対するMRMトランジションは一つであるとは限らず、複数である場合もある。
図2(a1)に示した例では、五種類の化合物A、B、C、D、Eに対応するMRMトランジションについて、最適なノズル電圧がそれぞれ+2、+4、+3、+1、+4[kV]と求まる。
図2(a)はMRM測定対象のイオンの極性が全て正である例であるが、図2(b)はMRM測定対象のイオンの極性が全て負である例である。印加電圧の絶対値が小さいものから順に大きくなるように測定の順序が並べ替えられるため、この例では、ノズル電圧が-1→-2→-2.5→-3[kV]となるように並替えが行われている。
2…第1中間真空室
3…第2中間真空室
4…分析室
5…ESI用プローブ
6…加熱キャピラリ
8…スキマー
7、9…イオンガイド
10…前段四重極マスフィルタ
11…コリジョンセル
12…多重極イオンガイド
13…後段四重極マスフィルタ
14…イオン検出器
20…高電圧電源
21…データ処理部
30…制御部
31…分析制御部
32…分析シーケンス決定部
33…分析条件設定処理部
34…測定順序並替え部
35…分析シーケンス記憶部
36…入力部
37…表示部
Claims (5)
- 試料中の化合物をイオン化するイオン源、化合物由来のイオンを質量電荷比に応じて分離する質量分離部、及び、質量電荷比に応じて分離されたイオンを検出する検出部、を具備し、測定対象のイオンが異なる複数の選択イオンモニタリング(SIM)測定、又は、測定対象であるプリカーサイオンとプロダクトイオンとの組み合わせであるMRMトランジションが異なる複数の多重反応モニタリング(MRM)測定を行うサイクルを繰り返し実行する質量分析装置において、
a)任意の測定時間範囲内の1サイクル中に実行される複数のSIM測定対象のイオン又は複数のMRM測定対象のトランジションについての情報を収集する情報収集部と、
b)1サイクル中で異なるイオンに対するSIM測定又は異なるMRMトランジションに対するMRM測定を実行する順序を決定する測定順序決定部であって、前記情報収集部により収集された1サイクル中の複数のSIM測定対象のイオン又は複数のMRM測定対象のMRMトランジションに対する測定を、それらイオン又はMRMトランジションにそれぞれ好適な前記イオン源への印加電圧の極性毎に集約したうえで、同じ極性の中で前記印加電圧の絶対値に従って測定の順序を並べ替えることで1サイクル中の測定順序を決定する測定順序決定部と、
を備えることを特徴とする質量分析装置。 - 請求項1に記載の質量分析装置であって、
前記測定順序決定部は、同じ極性の中で前記印加電圧の絶対値が低いものから順に高くなるように測定の順序を並べ替えることを特徴とする質量分析装置。 - 請求項1又は2に記載の質量分析装置であって、
前記測定順序決定部により決定された測定順序に従ってSIM測定又はMRM測定を実行するように各部を制御する制御部をさらに備えることを特徴とする質量分析装置。 - 請求項1~3のいずれか1項に記載の質量分析装置であって、
前記情報収集部は、1サイクル中に実行したい複数のSIM測定対象イオン又は複数のMRMトランジションを分析者が指定する情報指定部を含むことを特徴とする質量分析装置。 - 請求項1~4のいずれか1項に記載の質量分析装置であって、
前記イオン源は、試料溶液を帯電させつつ大気雰囲気中に噴霧するノズルを含むエレクトロスプレーイオン化法によるイオン源であり、前記印加電圧は前記ノズルに印加される電圧であることを特徴とする質量分析装置。
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