ANALYZING TARGET ANALYTES IN A SAMPLE USING MASS SPECTROSCOPY

• US 20130306853A1
• Filed: 05/16/2013
• Published: 11/21/2013
• Est. Priority Date: 05/17/2012
• Status: Active Grant

• Current Assignee: Micromass UK Ltd (Waters Corporation)
• Original Assignee: Micromass UK Ltd (Waters Corporation)
• Inventors: Eastwood, Martin
• Granted Patent: US 8,993,958 B2
• Time in Patent Office: Days
• US Class Current: 250/282
• CPC Class Codes: G01N 33/6851 Methods of protein analysis involving laser desorption ionisation mass spectrometry
• CPC Class Codes: G01N 33/743 Steroid hormones
• CPC Class Codes: H01J 49/0036 Step by step routines describing the handling of the data generated during a measurement
• CPC Class Codes: H01J 49/04 Arrangements for introducing or extracting samples to be analysed, e.g. vacuum locks; Arrangements for external adjustment of electron- or ion-optical components

Abstract

A method for determining an amount of an analyte in a sample by mass spectrometry can include the steps of (i) ionizing an analyte from the sample and a deuterated analog of the analyte, to produce an analyte ion and a deuterated analog ion, where the deuterated analog undergoes fragmentation and deuterium scattering during mass spectrometry; (ii) measuring an analyte ion signal and a deuterated analog ion signal by mass spectrometry, where the deuterated analog ion signal is measured using a mass transition resulting from fragmentation and deuterium scattering; and (iii) determining an amount of analyte in the sample using the analyte ion signal and the deuterated analog ion signal. Corresponding kits can include instructions for carrying out the method, together with a deuterated analog of the analyte selected to undergo fragmentation and deuterium scattering during mass spectrometry and exhibit a mass transition resulting from fragmentation and deuterium scattering.

Claims

1. A method for determining an amount of an analyte in a sample by mass spectrometry, the method comprising:

ionizing an analyte from the sample and a deuterated analog of the analyte, to produce an analyte ion and a deuterated analog ion, wherein the deuterated analog undergoes fragmentation and deuterium scattering during mass spectrometry;

measuring an analyte ion signal and a deuterated analog ion signal by mass spectrometry, wherein the deuterated analog ion signal is measured using a mass transition resulting from fragmentation and deuterium scattering; and

determining an amount of analyte in the sample using the analyte ion signal and the deuterated analog ion signal.

2. The method of claim 1, wherein the mass spectrometry comprises collision induced dissociation (CID) mass spectrometry.

3. The method of claim 1, wherein the deuterated analog ion comprises a fragment ion.

4. The method of claim 3, wherein the fragmentation and deuterium scattering result in the rearrangement of at least one deuterium atom from the fragment ion to a water molecule.

5. The method of claim 3, wherein the fragmentation and deuterium scattering result in the rearrangement of at least one deuterium atom from the fragment ion to a second fragment ion.

6. The method of claim 3, wherein the fragmentation and deuterium scattering result in the rearrangement of at least one deuterium atom from a second fragment ion to the fragment ion.

7. The method of claim 1, wherein the deuterated analog further comprises a non-hydrogen stable isotope label.

8. A method for determining an amount of cortisol in a sample by mass spectrometry, the method comprising:

ionizing cortisol from the sample and a deuterated cortisol analog, to produce a cortisol ion and a deuterated cortisol analog ion, wherein the deuterated cortisol analog undergoes fragmentation and deuterium scattering during mass spectrometry;

measuring a cortisol ion signal and a deuterated cortisol analog ion signal by mass spectrometry, wherein the deuterated cortisol analog ion signal is measured using a mass transition resulting from fragmentation and deuterium scattering; and

determining an amount of cortisol in the sample using the cortisol ion signal and the deuterated cortisol ion signal.

9. The method of claim 8, wherein the deuterated cortisol analog comprises d4-cortisol.

10. The method of claim 9, wherein the mass transition comprises an m/z of about 367>

312.

11. The method of claim 8, wherein the deuterated cortisol analog comprises d2-cortisol.

12. The method of claim 11, wherein the mass transition comprises an m/z of about 365>

312.

13. A kit for determining an amount of an analyte in a sample by mass spectrometry, the kit comprising:

a deuterated analog of the analyte, the deuterated analog selected to undergo fragmentation and deuterium scattering during mass spectrometry and exhibit a mass transition resulting from fragmentation and deuterium scattering; and

instructions for (i) ionizing an analyte from the sample and a deuterated analog of the analyte, to produce a analyte ion and a deuterated analog ion, (ii) measuring an analyte ion signal and a deuterated analog ion signal by mass spectrometry, wherein the deuterated analog ion signal is measured using the mass transition resulting from fragmentation and deuterium scattering, and (iii) determining an amount of analyte in the sample using the analyte ion signal and the deuterated analog ion signal.

14. The kit of claim 13, wherein the mass spectrometry comprises collision induced dissociation (CID) mass spectrometry.

15. The kit of claim 13, wherein the deuterated analog ion comprises a fragment ion.

16. The kit of claim 13, wherein the fragmentation and deuterium scattering result in the rearrangement of at least one deuterium atom from the fragment ion to a water molecule.

17. The kit of claim 13, wherein the fragmentation and deuterium scattering result in the rearrangement of at least one deuterium atom from the fragment ion to a second fragment ion.

18. The kit of claim 13, wherein the fragmentation and deuterium scattering result in the rearrangement of at least one deuterium atom from a second fragment ion to the fragment ion.

19. The kit of claim 13, wherein the deuterated analog further comprises a non-hydrogen stable isotope label.

20. The kit of claim 13, wherein the deuterated analog comprises a d4-cortisol and the mass transition comprises an m/z of about 367>

312.

21. The kit of claim 13, wherein the deuterated analog comprises a d2-cortisol and the mass transition comprises an m/z of about 365>

312.