Method of screening a sample for the presence of one or more known compounds of interest and a mass spectrometer performing this method

Patent metadata

Field	Value
Publication number	US-9779929-B2
Application number	US-201414472587-A
Country	US
Kind code	B2
Filing date	Aug 29, 2014
Priority date	Sep 4, 2009
Publication date	Oct 3, 2017
Grant date	Oct 3, 2017

Abstract

A method of screening a sample for the presence of one or more known compounds of interest is disclosed. A fragmentation device is repeatedly switched between a fragmentation mode of operation and a non-fragmentation mode of operation. A determination is made whether a candidate parent ion of interest is present in a non-fragmentation data set and whether one or more corresponding fragment ions of interest are present in a fragmentation data set. A further determination is made to check if the candidate parent ion of interest and the one or more corresponding fragment ions of interest have substantially similar elution or retention times and/or ion mobility drift times.

First claim

The invention claimed is:

1. A method of screening a sample for a presence of one or more known compounds of interest with a mass spectrometer comprising a fragmentation, collision or reaction device and a mass analyser, said method comprising:
repeatedly switching said fragmentation, collision or reaction device between a first mode of operation and a second mode of operation, wherein in said first mode of operation parent ions are not substantially fragmented within said fragmentation, collision or reaction device or are arranged to bypass said fragmentation, collision or reaction device and are then subsequently mass analysed by said mass analyser and wherein in said second mode of operation parent ions are substantially fragmented within said fragmentation, collision or reaction device to form a plurality of fragment ions which are then subsequently mass analysed by said mass analyser;
selecting a known compound of interest, and identifying a candidate parent ion of interest associated with said known compound of interest;
determining if said candidate parent ion of interest is present in a first data set obtained when said fragmentation, collision or reaction device was operated in said first mode of operation; and
determining if one or more fragment ions of interest corresponding to said candidate parent ion of interest are present in a second data set obtained when said fragmentation, collision or reaction device was operated in said second mode of operation;
wherein if said candidate parent ion of interest is determined to be present in said first data set and one or more corresponding fragment ions of interest are also determined to be present in said second data set then said method further comprises determining whether or not said candidate parent ion of interest and said one or more fragment ions of interest have substantially similar elution or retention times or ion mobility drift times;
wherein if said candidate parent ion of interest and said one or more fragment ions of interest are determined to have substantially similar elution or retention times or ion mobility drift times then a determination is made that said known compound of interest is present in said sample.

2. A method as claimed in claim 1 , wherein said mass analyser comprises a Time of Flight mass analyser, a Fourier Transform Ion Cyclotron Resonance mass analyser or an electrostatic orbital mass analyser.

3. A method as claimed in claim 1 , wherein said elution or retention time comprises an elution or retention time from a chromatographic column.

4. A method as claimed in claim 1 , wherein said ion mobility drift times correspond with ion mobility drift times of ions through an ion mobility spectrometer or separator arranged upstream of said fragmentation, collision or reaction device.

5. A method as claimed in claim 1 , wherein said fragmentation, collision or reaction device comprises a Collision Induced Dissociation fragmentation device, an Electron Transfer Dissociation fragmentation device, an Electron Capture Dissociation fragmentation device or a Surface Induced Dissociation fragmentation device.

6. A method as claimed in claim 1 , wherein if said candidate parent ion of interest and said one or more fragment ions of interest are determined to have substantially different elution or retention times or ion mobility drift times then said candidate parent ion of interest is rejected, downgraded in status or reduced in significance as a candidate parent ion of interest.

7. A method as claimed in claim 1 , wherein if said candidate parent ion of interest is determined to have a lower charge state that one or more of said corresponding fragment ions of interest then said candidate parent ion of interest is rejected, downgraded in status or reduced in significance as a candidate parent ion of interest.

8. A method as claimed in claim 1 , wherein if said candidate parent ion of interest is determined to have an unexpected isotopic distribution then said candidate parent ion of interest is rejected, downgraded in status or reduced in significance as a candidate parent ion of interest.

9. A method as claimed in claim 1 , wherein if fragment ions of interest corresponding with said candidate parent ion of interest are determined to have an unexpected isotopic distribution then said candidate parent ion of interest is rejected, downgraded in status or reduced in significance as a candidate parent ion of interest.

10. A method as claimed in claim 1 , wherein if said candidate parent ion of interest or corresponding fragment ions of interest are determined to have an elution or retention time falling outside of an expected time window then said candidate parent ion of interest is rejected, downgraded in status or reduced in significance as a candidate parent ion of interest.

11. A method as claimed in claim 1 , wherein if said candidate parent ion of interest or corresponding fragment ions of interest are determined to have an ion mobility drift time falling outside of an expected time window then said candidate parent ion of interest is rejected, downgraded in status or reduced in significance as a candidate parent ion of interest.

12. A method as claimed in claim 1 , wherein if a ratio of an intensity of said candidate parent ion of interest to one or more of said fragment ions of interest falls outside an expected range then said candidate parent ion of interest is rejected, downgraded in status or reduced in significance as a candidate parent ion of interest.

13. A method as claimed in claim 1 , further comprising determining an intensity of or quantifying said known compound of interest.

14. A method of screening a sample for a presence of one or more known compounds of interest with a mass spectrometer comprising a fragmentation, collision or reaction device and a mass analyser, said method comprising:
repeatedly switching said fragmentation, collision or reaction device between a first mode of operation and a second mode of operation, wherein in said first mode of operation parent ions are not substantially fragmented within said fragmentation, collision or reaction device or are arranged to bypass said fragmentation, collision or reaction device and are then subsequently mass analysed by said mass analyser and wherein in said second mode of operation parent ions are substantially fragmented within said fragmentation, collision or reaction device to form a plurality of fragment ions which are then subsequently mass analysed by said mass analyser;
selecting a known compound of interest, and identifying one or more fragment ions of interest associated with said known compound of interest;
determining if said one or more fragment ions of interest are present in a second data set obtained when second fragmentation, collision or reaction device was operated in said second mode of operation;
determining if a candidate parent ion of interest corresponding to said one or more fragment ions of interest is present in a first data set obtained when said fragmentation, collision or reaction device was operated in said first mode of operation;
wherein if said one or more fragment ions of interest are determined to be present in said second data set and said corresponding candidate parent ion of interest is also determined to be present in said first data set then said method further comprises determining whether or not said candidate parent ion of interest and said one or more fragment ions of interest have substantially similar elution or retention times or ion mobility drift times;
wherein if said candidate parent ion of interest and said one or more fragment ions of inter

Assignees

• Micromass Ltd

Inventors

• Goshawk Jeffrey Alan
• Pringle Steven Derek
• Smith Steve

Classifications

• H01J49/004

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

• H01J49/40 Primary

  Time-of-flight spectrometers (H01J49/36 takes precedence) · CPC title

• H01J49/0027 Primary

  Methods for using particle spectrometers · CPC title

• G01N30/72

  Mass spectrometers {(mass spectrometers per se H01J49/00)} · CPC title