Scheduled MS3 for quantitation

Patent metadata

Field	Value
Publication number	US-9548190-B2
Application number	US-201314443930-A
Country	US
Kind code	B2
Filing date	Nov 21, 2013
Priority date	Dec 20, 2012
Publication date	Jan 17, 2017
Grant date	Jan 17, 2017

Abstract

Systems and methods are provided for scheduled MS 3 . A compound of interest is separated from a sample over a known time period using a separation device. A plurality of sMRM experiments are performed over the known time period on the separating compound of interest using a mass spectrometer. An intensity of a product ion of the compound of interest is produced for each of the plurality of sMRM experiments. Each intensity for the product ion for each of the plurality of sMRM experiments is compared to a threshold intensity level using a processor. When an intensity for the product ion of an sMRM experiment of the plurality of sMRM experiments is equal to or exceeds the threshold intensity level, the mass spectrometer is instructed to perform one or more MS 3 experiments for the product ion using the processor.

First claim

What is claimed is:

1. A system for scheduled mass spectrometry/mass spectrometry/mass spectrometry (MS 3 ), comprising:
a separation device that separates a compound of interest from a sample over a known time period;
a mass spectrometer that performs a plurality of scheduled multiple reaction monitoring (sMRM) experiments over the known time period on the separating compound of interest, producing an intensity of a product ion of the compound of interest for each of the plurality of sMRM experiments; and
a processor in communication with the mass spectrometer and the separation device that is configured to
receive each intensity for the product ion for each of the plurality of sMRM experiments from the mass spectrometer,
compare each intensity for the product ion for each of the plurality of sMRM experiments to a threshold intensity level, and
when an intensity for the product ion of an sMRM experiment of the plurality of sMRM experiments is equal to or exceeds the threshold intensity level, instruct the mass spectrometer to perform one or more MS 3 experiments for the product ion, producing intensities of one or more secondary fragment ions of the compound of interest for each of the one or more MS 3 experiments,

wherein each sMRM experiment of the plurality of sMRM experiments is scheduled during a predicted or known elution time of the separating compound of interest, and
wherein the one or more MS 3 experiments comprise a cycle of MS 3 experiments that provide a number of intensities of the secondary fragment ions over time to quantify the compound of interest in the sample.

2. The system of claim 1 , wherein the processor is further configured to identify the compound of interest from an intensity of the secondary fragment ion produced by the one or more MS 3 experiments.

3. The system of claim 1 , wherein the number of intensities of the secondary fragment ions over time to quantify the compound of interest in the sample comprises
a number to provide a representative of a liquid chromatography (LC) peak shape for the secondary fragment ion.

4. The system of claim 1 , wherein the processor is configured to instruct the mass spectrometer to stop the sMRM experiments when an intensity for the product ion of an sMRM experiment of the plurality of sMRM experiments first reaches a level that is equal to or greater than the threshold intensity level, thereby halting the plurality of sMRM experiments as soon as the one or more MS 3 experiments are triggered.

5. The system of claim 1 , wherein the processor is configured to instruct the mass spectrometer to perform one or more MS 3 experiments for the product ion only when a first intensity for the product ion of an sMRM experiment of the plurality of sMRM experiments is equal to or exceeds the threshold intensity level to prevent another group of one or more MS 3 experiments being triggered for a time period of separation.

6. The system of claim 1 , wherein the processor is further configured to determine, after instructing the mass spectrometer to perform one or more MS 3 experiments for the product ion, when an intensity for the product ion of an sMRM experiment of the plurality of sMRM experiments is less than the threshold intensity level, instructs the mass spectrometer to stop MS 3 experiments for the product ion.

7. A method for scheduled mass spectrometry/mass spectrometry/mass spectrometry (MS 3 ), comprising:
separating a compound of interest from a sample over a known time period using a separation device;
performing a plurality of scheduled multiple reaction monitoring (sMRM) experiments over the known time period on the separating compound of interest using a mass spectrometer, producing an intensity of a product ion of the compound of interest for each of the plurality of sMRM experiments, wherein each sMRM experiment of the plurality of sMRM experiments is scheduled during a predicted or known elution time of the separating compound of interest;
receiving each intensity for the product ion for each of the plurality of sMRM experiments from the mass spectrometer using a processor;
comparing each intensity for the product ion for each of the plurality of sMRM experiments to a threshold intensity level using the processor, and
when an intensity for the product ion of an sMRM experiment of the plurality of sMRM experiments is equal to or exceeds the threshold intensity level, instructing the mass spectrometer to perform one or more MS 3 experiments for the product ion using the processor, producing intensities of one or more secondary fragment ions of the compound of interest for each of the one or more MS 3 experiments,
wherein the one or more MS 3 experiments comprise a cycle of MS 3 experiments that provide a number of intensities of the secondary fragment ions over time to quantify the compound of interest in the sample.

8. The method of claim 7 , further comprising identifying the compound of interest from an intensity of the secondary fragment ion produced by the one or more MS 3 experiments using the processor.

9. The method of claim 7 , wherein the number of intensities of the secondary fragment ions over time to quantify the compound of interest in the sample comprises
a number to provide a representative of a liquid chromatography (LC) peak shape for the secondary fragment ion.

10. The method of claim 7 , further comprising instructing the mass spectrometer to stop the sMRM experiments when an intensity for the product ion of an sMRM experiment of the plurality of sMRM experiments first reaches a level that is equal to or greater than the threshold intensity level, thereby halting the plurality of sMRM experiments as soon as the one or more MS 3 experiments are triggered.

11. The method of claim 7 , further comprising instructing the mass spectrometer to perform one or more MS 3 experiments for the product ion only when a first intensity for the product ion of an sMRM experiment of the plurality of sMRM experiments is equal to or exceeds the threshold intensity level using the processor, to prevent another group of one or more MS 3 experiments being triggered for a time period of separation.

12. The method of claim 7 , further comprising after instructing the mass spectrometer to perform one or more MS 3 experiments for the product ion, determining when an intensity for the product ion of an sMRM experiment of the plurality of sMRM experiments is less than the threshold intensity level using the processor and instructing the mass spectrometer to stop MS 3 experiments for the product ion when an intensity for the product ion of an sMRM experiment of the plurality of sMRM experiments is less than the threshold intensity level using the processor.

13. A computer program product, comprising a non-transitory and tangible computer-readable storage medium whose contents include a program with instructions being executed on a processor so as to perform a method for scheduled mass spectrometry/mass spectrometry/mass spectrometry (MS 3 ), the method comprising:
providing a system, wherein the system comprises one or more distinct software modules, and wherein the distinct software modules comprise an analysis module and a control module;
receiving an intensity for a product ion for each of a plurality of scheduled multiple reaction monitoring (sMRM) experiments the plurality of sMRM experiments from a mass spectrometer using the analysis module, wherein each intensity for the product ion of each of the plurality of sMRM experiments is produced by performing the plurality of sMRM experiments over a known time period on a separating compound of interest using a mass spect

Assignees

• Dh Technologies Dev Pte Ltd

Inventors

• Campbell John Lawrence
• Cox David Michael

Classifications

• H01J49/004 Primary

  Combinations of spectrometers, tandem spectrometers, e.g. MS/MS, MSn · CPC title

• H01J49/022

  Circuit arrangements, e.g. for generating deviation currents or voltages (regulating electric or magnetic variables in general, e.g. current, magnetic field G05F); Components associated with high voltage supply (high voltage supply per se H02M) · CPC title

• H01J49/0081 Primary

  Tandem in time, i.e. using a single spectrometer · CPC title

• H01J49/0036

  Step by step routines describing the handling of the data generated during a measurement · CPC title