Dual single-ion monitoring mass spectrometry

Abstract

The present invention relates to a method for determining an analyte in a mass spectrometer (MS) apparatus comprising first and second mass filters, the method comprising: (i) filtering an analyte ion species in a first mass filter; (ii) optionally fragmenting at least a portion of the ions obtained by filtering in step (i) in a collision cell, wherein the collision energy of the fragmentation is selected to be lower than a predetermined collision energy that causes the fragmentation of the analyte ion species; (iii) filtering the analyte ion species filtered in step (i) in a second mass filter; and (iv) detecting the analyte ion species filtered in step (iii) to determine the analyte. Furthermore, the present invention relates to apparatus, systems, and uses related to the method.

Claims

1. A method for determining an analyte in a mass spectrometer (MS) apparatus comprising a first mass filter, a second mass filter, and a collision cell, (i) filtering out analyte ion species in the first mass filter, (ii) Fragmenting in the collision cell, wherein at least a portion of the ions obtained by the filtering in step (i) is selected such that the collision energy of the fragmentation is lower than a predetermined collision energy that causes the fragmentation of the analyte ion species. (iii) Filtering the analyte ion species in the second mass filter, A method comprising (iv) detecting the analyte ion species filtered in step (iii) and thereby determining the analyte.

2. The method according to claim 1, wherein the sample is a biological sample, in one embodiment a sample of a subject's bodily fluids, in a further embodiment blood or a blood-derived sample, and in one embodiment a serum sample.

3. The method according to claim 1 or 2, wherein the analyte is an organic compound, in one embodiment being a metabolite of a subject, and in a further embodiment being estradiol.

4. The method according to any one of claims 1 to 3, wherein the MS apparatus comprises three quadrupoles.

5. The method according to claim 4, wherein in step (i), a first quadrupole is used as the first mass filter, in step (ii), a second quadrupole is used as the collision cell, and in step (iii), a third quadrupole is used as the second mass filter.

6. The method according to any one of claims 1 to 5, wherein the predetermined collision energy is a collision energy that causes fragmentation of at least 90%, at least 75% in one embodiment, and at least 50% in a further embodiment, and in one embodiment, is the optimal collision energy for the same analyte ion species in a multiple reaction measurement.

7. The method according to any one of claims 1 to 6, wherein the collision energy selected in step (ii) is up to 50%, up to 75% in one embodiment, up to 80% in a further embodiment, and up to 90% in a further embodiment.

8. The method according to any one of claims 1 to 6, wherein the collision energy selected in step (ii) is 50% to 90% of the predetermined collision energy, and in one embodiment, 50% to 80%.

9. The method according to any one of claims 1 to 6, wherein the collision energy selected in step (ii) is 70% to 90% of the predetermined collision energy, and in one embodiment, 70% to 80%.

10. The method according to any one of claims 1 to 9, wherein the filtering in step (iii) is narrow-pass filtering.

11. The method according to claim 10, wherein the narrow-pass filtering is filtering for ions with m / z values ​​within a range of ±2 centered on the m / z value of the analyte ion species.

12. The method according to any one of claims 1 to 11, wherein up to 30%, up to 20%, and up to 10% of the analyte ions passing through the first mass filter are fragmented at the second quadrupole.

13. The method according to any one of claims 1 to 12, wherein the determination in step (iv) is based on detecting the analyte ion species as the only ion species determined.

14. The method according to any one of claims 1 to 13, further comprising a sample pretreatment step, wherein in one embodiment the sample pretreatment step comprises immunoconcentration and / or chromatography of the sample.

15. The method according to any one of claims 1 to 14, wherein the sample pretreatment step comprises mixing an internal standard with the sample, and in one embodiment the internal standard is an isotopolog of the analyte.

16. The method according to any one of claims 1 to 15, wherein in step (iv), specifically, ion species within a range of ±0.7% of the analyte ion species, within a range of ±0.3% of the analyte ion species in one embodiment, and within a range of ±0.2% of the analyte ion species in a further embodiment.

17. The method according to any one of claims 1 to 16, wherein the analyte is a small molecule compound having a maximum molecular mass of 1000 u (1 kDa).

18. (I) A first quadrupole adapted to function as a first mass filter, (II) A second quadrupole adapted to function as a collision cell, (III) A third quadrupole adapted to function as a second mass filter, (IV) A control unit equipped with a microprocessor, and an MS device comprising MS device, wherein the control unit comprises tangibly incorporated executable code that, when executed by the microcontroller, causes the device to perform the method according to any one of claims 1 to 17.

19. The MS apparatus according to claim 18, further comprising a memory unit having a database having at least one analyte identifier assigned to at least one value of at least one method parameter.

20. The MS apparatus according to claim 18 or 19, wherein the at least one method parameter is selected from the m / z value of the analyte ion species, the molecular mass of the analyte ion species, and / or the collision energy.

21. An analytical system comprising an MS apparatus according to any one of claims 11 to 13 and a chromatography apparatus.

22. Use of an MS apparatus according to any one of claims 18 to 21 for determining analytes in a sample.

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