COMPOSITIONS, METHODS, AND KITS FOR QUANTIFYING TARGET ANALYTES IN A SAMPLE

• US 20140158881A1
• Filed: 06/06/2012
• Published: 06/12/2014
• Est. Priority Date: 06/06/2011
• Status: Active Grant

• Current Assignee: Waters Technologies Corporation (Waters Corporation)
• Original Assignee: Waters Technologies Corporation (Waters Corporation)
• Inventors: Cooper, Donald P.
• Granted Patent: US 9,768,001 B2
• Time in Patent Office: Days
• US Class Current: 250/282
• CPC Class Codes: G01N 2030/045 internal
• CPC Class Codes: G01N 30/72 Mass spectrometers mass spectrometers per se H01J49/00
• CPC Class Codes: G01N 30/8665 for calibrating the measuring apparatus
• CPC Class Codes: H01J 49/0009 Calibration of the apparatus

Abstract

A method of quantifying a target analyte by mass spectrometry includes obtaining a mass spectrometer signal comprising a first calibrator signal, comprising a second calibrator signal, and potentially comprising a target analyte signal from a single sample comprising a first known quantity of a first calibrator, comprising a second known quantity of a second calibrator, and potentially comprising a target analyte. The first known quantity and the second known quantity are different, and wherein the first calibrator, the second calibrator, and the target analyte are each distinguishable in the single sample by mass spectrometry. The method also includes quantifying the target analyte in the single sample using the first calibrator signal, the second calibrator signal, and the target analyte signal.

Claims

1. A method of quantifying a target analyte by mass spectrometry, the method comprising:

obtaining a mass spectrometer signal comprising a first calibrator signal, comprising a second calibrator signal, and potentially comprising a target analyte signal from a single sample comprising a first known quantity of a first calibrator, comprising a second known quantity of a second calibrator, and potentially comprising a target analyte,

wherein the first known quantity and the second known quantity are different, and wherein the first calibrator, the second calibrator, and the target analyte are each distinguishable in the single sample by mass spectrometry; and

quantifying the target analyte in the single sample using the first calibrator signal, the second calibrator signal, and the target analyte signal.

2. The method of claim 1, further comprising:

preparing the single sample by combining the first known quantity of the first calibrator and the second known quantity of the second calibrator in a single specimen potentially comprising the target analyte; and

generating the mass spectrometer signal from the single sample using a mass spectrometer.

3. The method of claim 1, further comprising:

separating the first calibrator, the second calibrator, and the target analyte from other components of the single sample prior to obtaining the mass spectrometer signal.

4. The method of claim 3, wherein the separation comprises chromatography and the first calibrator, the second calibrator, and the target analyte co-elute.

5. The method of claim 3, wherein the separation comprises chromatography and the first calibrator, the second calibrator, and the target analyte elute separately.

6. The method of claim 3, wherein the separation comprises at least one of solid phase extraction, liquid chromatography, gas chromatography, affinity, immunoaffinity, and supercritical fluid chromatography.

7. The method of claim 1, wherein quantifying the target analyte comprises:

obtaining a calibration curve from the first calibrator signal and the second calibrator signal; and

quantifying the target analyte using the calibration curve and the target analyte signal.

8. The method of claim 1, wherein quantifying the target analyte comprises:

quantifying the target analyte algebraically using the first calibrator signal, the second calibrator signal, and the target analyte signal.

9. The method of claim 1, wherein the first calibrator and the second calibrator are each different stable isotope analogs of the target analyte.

10. The method of claim 1, wherein the first calibrator and the second calibrator are each different analogs, derivatives, metabolites, or related compounds of the target analyte.

11. The method of claim 1, further comprising:

obtaining, from the mass spectrometer signal, a third calibrator signal, a fourth calibrator signal, and an additional target analyte signal from the single sample comprising a third known quantity of a third calibrator, comprising a fourth known quantity of a fourth calibrator, and potentially comprising an additional target analyte,

wherein the third known quantity and the fourth known quantity are different, and wherein the first calibrator, the second calibrator, the third calibrator, the fourth calibrator, the target analyte, and the additional target analyte are each distinguishable in the single sample by mass spectrometry; and

quantifying the additional target analyte in the single sample using the third calibrator signal, the fourth calibrator signal, and the additional target analyte signal.

12. The method of claim 11, further comprising:

obtaining, from the mass spectrometer signal, a fifth calibrator signal, a sixth calibrator signal, and a second additional target analyte signal from the single sample comprising a fifth known quantity of a fifth calibrator, comprising a sixth known quantity of a sixth calibrator, and potentially comprising a second additional target analyte,

wherein the fifth known quantity and the sixth known quantity are different, and wherein the first calibrator, the second calibrator, the third calibrator, the fourth calibrator, the fifth calibrator, the sixth calibrator, the target analyte, the additional target analyte, and the second additional target analyte are each distinguishable in the single sample by mass spectrometry; and

quantifying the second additional target analyte in the single sample using the fifth calibrator signal, the sixth calibrator signal, and the second additional target analyte signal.

13. The method of claim 1, further comprising:

obtaining, from the mass spectrometer signal, a third calibrator signal from the single sample further comprising a third known quantity of a third calibrator,

wherein the first known quantity, the second known quantity, and the third known quantity are different, and wherein the first calibrator, the second calibrator, the third calibrator, and the target analyte are each distinguishable in the single sample by mass spectrometry, and

wherein quantifying the target analyte further comprises using the third calibrator.

14. The method of claim 13, further comprising:

obtaining, from the mass spectrometer signal, a fourth calibrator signal from the single sample further comprising a fourth known quantity of a fourth calibrator,

wherein the first known quantity, the second known quantity, the third known quantity, and the fourth known quantity are different, and wherein the first calibrator, the second calibrator, the third calibrator, the fourth calibrator and the target analyte are each distinguishable in the single sample by mass spectrometry, and

wherein quantifying the target analyte further comprises using the fourth calibrator.

15. A composition for quantifying a target analyte by mass spectrometry comprising:

a first known quantity of a first calibrator and a second known quantity of a second calibrator, wherein the first known quantity and the second known quantity are different, and wherein the first calibrator, the second calibrator, and the target analyte are each distinguishable in the single sample by mass spectrometry.

16. The composition of claim 15, wherein the first calibrator and the second calibrator are each different stable isotope analogs, analogs, derivatives, metabolites, or related compounds of the target analyte.

17. The composition of claim 15, further comprising:

a third known quantity of a third calibrator and a fourth known quantity of a fourth calibrator, wherein the third known quantity and the fourth known quantity are different, and wherein the first calibrator, the second calibrator, the third calibrator, the fourth calibrator, the target analyte, and the additional target analyte are each distinguishable in the single sample by mass spectrometry.

18. The composition of claim 17, further comprising:

a fifth known quantity of a fifth calibrator and a sixth known quantity of a sixth calibrator, wherein the fifth known quantity and the sixth known quantity are different, and wherein the first calibrator, the second calibrator, the third calibrator, the fourth calibrator, the fifth calibrator, the sixth calibrator, the target analyte, the additional target analyte, and the second additional target analyte are each distinguishable in the single sample by mass spectrometry.

19. The composition of claim 15, further comprising:

a third known quantity of a third calibrator, wherein the first known quantity, the second known quantity, and the third known quantity are different, and wherein the first calibrator, the second calibrator, the third calibrator, and the target analyte are each distinguishable in the single sample by mass spectrometry.

20. The composition of claim 19, further comprising:

a fourth known quantity of a fourth calibrator, wherein the first known quantity, the second known quantity, the third known quantity, and the fourth known quantity are different, and wherein the first calibrator, the second calibrator, the third calibrator, the fourth calibrator, and the target analyte are each distinguishable in the single sample by mass spectrometry.

21. The composition of claim 15, further comprising:

a sample holder defining at least one sample receptacle, wherein the first known quantity of the first calibrator and the second known quantity of the second calibrator are both comprised within the at least one sample receptacle.

22. The composition of claim 17, further comprising:

a sample holder defining at least one sample receptacle, wherein the first known quantity of the first calibrator, the second known quantity of the second calibrator, the third known quantity of the third calibrator, and the fourth known quantity of the fourth calibrator are all comprised within the at least one sample receptacle.

23. A kit for quantifying a target analyte by mass spectrometry, the kit comprising:

a first known quantity of a first calibrator and a second known quantity of a second calibrator, wherein the first known quantity and the second known quantity are different, and wherein the first calibrator, the second calibrator, and the target analyte are each distinguishable in the single sample by mass spectrometry; and

instructions for (i) obtaining a mass spectrometer signal comprising a first calibrator signal, a second calibrator signal, and a target analyte signal from a single sample comprising the first known quantity of the first calibrator, comprising the second known quantity of the second calibrator, and potentially comprising the target analyte and (ii) quantifying the target analyte in the single sample using the first calibrator signal, the second calibrator signal, and the target analyte signal.

24. The kit of claim 23, wherein the first calibrator and the second calibrator are each different stable isotope analogs, analogs, derivatives, metabolites, or related compounds of the target analyte.

25. The kit of claim 23, further comprising:

a third known quantity of a third calibrator and a fourth known quantity of a fourth calibrator, wherein the third known quantity and the fourth known quantity are different, and wherein the first calibrator, the second calibrator, the third calibrator, the fourth calibrator, the target analyte, and the additional target analyte are each distinguishable in the single sample by mass spectrometry; and

instructions for (i) obtaining, from a mass spectrometer, a third calibrator signal, a fourth calibrator signal, and an additional target analyte signal from a single sample comprising the third known quantity of the third calibrator, comprising the fourth known quantity of the fourth calibrator, and potentially comprising the additional target analyte and (ii) quantifying the additional target analyte in the single sample using the third calibrator signal, the fourth calibrator signal, and the additional target analyte signal.

26. The kit of claim 23, further comprising:

a sample holder defining at least one sample receptacle, wherein the first known quantity of the first calibrator and the second known quantity of the second calibrator are both comprised within the at least one sample receptacle.

27. The kit of claim 25, further comprising:

a sample holder defining at least one sample receptacle, wherein the first known quantity of the first calibrator, the second known quantity of the second calibrator, the third known quantity of the third calibrator, and the fourth known quantity of the fourth calibrator are all comprised within the at least one sample receptacle.

28. A computer readable medium comprising computer executable instructions adapted to:

obtain a mass spectrometer signal comprising a first calibrator signal, comprising a second calibrator signal, and potentially comprising a target analyte signal from a single sample comprising a first known quantity of a first calibrator, comprising a second known quantity of a second calibrator, and potentially comprising a target analyte,

wherein the first known quantity and the second known quantity are different, and wherein the first calibrator, the second calibrator, and the target analyte are each distinguishable in the single sample by mass spectrometry; and

quantify the target analyte in the single sample using the first calibrator signal, the second calibrator signal, and the target analyte signal.

29. The computer readable medium of claim 28, further comprising computer executable instructions adapted to:

direct an automated code reader to determine a listing of one or more analytes to be tested for in a given specimen based upon a code associated with the given specimen; and

direct an automated calibrator system to combine the given specimen with a first known quantity of a first calibrator and a second known quantity of a second calibrator for each of the one or more analytes.

30. An apparatus for quantifying a target analyte by mass spectrometry, the apparatus comprising:

a sample handler configured to prepare the single sample by combining a first known quantity of a first calibrator and a second known quantity of a second calibrator in a single specimen potentially comprising a target analyte;

a mass spectrometer configured to generate a mass spectrometer signal comprising a first calibrator signal, comprising a second calibrator signal, and potentially comprising a target analyte signal from a single sample comprising a first known quantity of a first calibrator, comprising a second known quantity of a second calibrator, and potentially comprising a target analyte, wherein the first known quantity and the second known quantity are different, and wherein the first calibrator, the second calibrator, and the target analyte are each distinguishable in the single sample by mass spectrometry; and

a data processor configured to quantify the target analyte in the single sample using the first calibrator signal, the second calibrator signal, and the target analyte signal.

31. The apparatus of claim 30, further comprising:

a separation system configured to separate the first calibrator, the second calibrator, and the target analyte from other components of the single sample prior to obtaining a mass spectrometer signal.

32. The apparatus of claim 30, wherein the separation system comprises at least one of solid phase extraction, liquid chromatography, gas chromatography, affinity, immunoaffinity, and supercritical fluid chromatography equipment.

33. The apparatus of claim 30, wherein the sample handler further comprises:

an automated code reader configured to determine a listing of one or more analytes to be tested for in a given specimen based upon a code associated with the given specimen; and

an automated calibrator system configured to combine the given specimen with a first known quantity of a first calibrator and a second known quantity of a second calibrator for each of the one or more analytes.

34. The apparatus of claim 33, wherein the automated calibrator system is configured to deliver the given specimen to a sample receptacle comprising the first known quantity of the first calibrator and the second known quantity of the second calibrator for each of the one or more analytes.

35. The apparatus of claim 33, wherein the automated calibrator system is configured to deliver the first known quantity of the first calibrator and the second known quantity of the second calibrator for each of the one or more analytes to a sample receptacle comprising the given specimen.