Mass spectrometry method, chromatograph mass spectrometer, and program for mass spectrometry

Patent metadata

Field	Value
Publication number	US-9983180-B2
Application number	US-201515548261-A
Country	US
Kind code	B2
Filing date	Feb 4, 2015
Priority date	Feb 4, 2015
Publication date	May 29, 2018
Grant date	May 29, 2018

Abstract

A mass spectrometry method includes: creating a plurality of measurement conditions corresponding to all combinations of precursor-ion candidates generated from the target compound and collision-energy-value candidates; performing a product-ion scan measurement using each of the plurality of measurement conditions and performing a plurality of reference measurements for detecting a predetermined kind of ion generated from the target compound under the same condition, within an introduction time during which the target compound is introduced; creating a peak function, which is a function representing a change in the amount of introduction of the target compound into the mass spectrometer within the introduction time, based on the result of the reference measurement; creating a normalization function for normalizing the amount of introduction of the target compound within the introduction time, based on the peak function; and normalizing the intensity of product-ion spectra obtained by the product-ion scan measurements performed for all combinations.

First claim

The invention claimed is:

1. A mass spectrometry method for optimizing a condition of a multiple reaction monitoring measurement of a target compound contained in a sample using a chromatograph mass spectrometer including a chromatograph and a mass spectrometer having front and rear mass separators with a collision cell in between, the method comprising:
a) creating a plurality of measurement conditions corresponding to all combinations of one or more precursor-ion candidates generated from the target compound and one or more collision-energy-value candidates;
b) introducing the sample into the chromatograph mass spectrometer;
c) performing a product-ion scan measurement at least one time using each of the plurality of measurement conditions as well as performing, a plurality of times and under a same condition, a reference measurement for detecting a predetermined kind of ion generated from the target compound, within an introduction time during which the target compound isolated by a column in the chromatograph is introduced into the mass spectrometer;
d) creating a peak function, which is a function representing a change in an amount of introduction of the target compound into the mass spectrometer within the introduction time, based on a result of the reference measurement;
e) creating a normalization function for normalizing the amount of introduction of the target compound within the introduction time, based on the peak function; and
f) normalizing an intensity of product-ion spectra obtained by the product-ion scan measurements performed for all of the aforementioned combinations, using the normalization function.

2. The mass spectrometry method according to claim 1 , wherein the reference measurement is a selected ion monitoring measurement.

3. The mass spectrometry method according to claim 2 , wherein the reference measurement is performed at least one time within each of first and second halves of the introduction time.

4. The mass spectrometry method according to claim 3 , wherein the product-ion scan measurement is performed at least two times for each of all of the aforementioned combinations within the introduction time.

5. The mass spectrometry method according to claim 2 , wherein the product-ion scan measurement is performed at least two times for each of all of the aforementioned combinations within the introduction time.

6. The mass spectrometry method according to claim 1 , wherein the reference measurement is performed at least one time within each of first and second halves of the introduction time.

7. The mass spectrometry method according to claim 6 , wherein the product-ion scan measurement is performed at least two times for each of all of the aforementioned combinations within the introduction time.

8. The mass spectrometry method according to claim 1 , wherein the product-ion scan measurement is performed at least two times for each of all of the aforementioned combinations within the introduction time.

9. A chromatograph mass spectrometer used for optimizing a condition of a multiple reaction monitoring measurement of a target compound contained in a sample, comprising:
a) a chromatograph having a column for isolating the target compound from other compounds;
b) a mass spectrometer having front and rear mass separators with a collision cell in between;
c) a measurement condition creator for creating a plurality of measurement conditions corresponding to all combinations of one or more precursor-ion candidates and one or more collision-energy-value candidates, based on a user input;
d) a measurement executor for performing a product-ion scan measurement at least one time under each of the plurality of measurement conditions as well as performing, a plurality of times and under a same condition, a reference measurement for detecting a predetermined kind of ion generated from the target compound, within an introduction time during which the target compound isolated by the column is introduced into the mass spectrometer;
e) a peak function creator for creating a peak function, which is a function representing a change in an amount of introduction of the target compound into the mass spectrometer within the introduction time, based on a result of the reference measurement;
f) a normalization function creator for creating a normalization function for normalizing the amount of introduction of the target compound within the introduction time, based on the peak function; and
g) a spectrum intensity normalizer for normalizing an intensity of product-ion spectra obtained by the product-ion scan measurements performed for all of the aforementioned combinations, using the normalization function.

10. A non-transitory computer readable medium recording a program for mass spectrometry used for optimizing a condition of a multiple reaction monitoring measurement of a target compound contained in a sample using a chromatograph mass spectrometer including a chromatograph and a mass spectrometer having front and rear mass separators with a collision cell in between, the program characterized by making a computer function as:
a) a measurement condition creator for creating a plurality of measurement conditions corresponding to all combinations of one or more precursor-ion candidates and one or more collision-energy-value candidates, based on a user input;
b) a measurement executor for performing a product-ion scan measurement at least one time under each of the plurality of measurement conditions as well as performing, a plurality of times, a reference measurement for detecting a predetermined kind of ion generated from the target compound under a same condition, within an introduction time during which the target compound isolated by the column is introduced into the mass spectrometer;
c) a peak function creator for creating a peak function, which is a function representing a change in an amount of introduction of the target compound into the mass spectrometer within the introduction time, based on a result of the reference measurement;
d) a normalization function creator for creating a normalization function for normalizing the amount of introduction of the target compound within the introduction time, based on the peak function; and
e) a spectrum intensity normalizer for normalizing an intensity of product-ion spectra obtained by the product-ion scan measurements performed for all of the aforementioned combinations, using the normalization function.

Assignees

• Shimadzu Corp

Inventors

• Sumiyoshi Takashi

Classifications

• G01N27/64

  using wave or particle radiation to ionise a gas, e.g. in an ionisation chamber · CPC title

• H01J49/26

  Mass spectrometers or separator tubes · CPC title

• G01N30/7233 Primary

  interfaced to liquid or supercritical fluid chromatograph (interfaces in general for introducing or extracting samples to be analysed with specially adapted mass spectrometer, see H01J49/04) · CPC title

• H01J49/0027 Primary

  Methods for using particle spectrometers · CPC title

• G01N30/8665

  for calibrating the measuring apparatus · CPC title