METHODS AND SYSTEMS FOR ANALYZING MEDICATION LEVELS IN A SAMPLE

• US 20100051801A1
• Filed: 09/02/2009
• Published: 03/04/2010
• Est. Priority Date: 09/03/2008
• Status: Active Grant

• Current Assignee: OREGON MEDICAL LABORATORIES
• Original Assignee: OREGON MEDICAL LABORATORIES
• Inventors: Erfurth, Stephen C., Beardsley, Grant D.
• Granted Patent: US 8,067,243 B2
• Time in Patent Office: Days
• US Class Current: 250/282
• CPC Class Codes: G01N 30/7233 interfaced to liquid or supercritical fluid chromatograph interfaces in general for introducing or extracting samples to be analysed with specially adapted mass spectrometer, see H01J49/04
• CPC Class Codes: G01N 33/48714 for determining substances foreign to the organism, e.g. drugs or heavy metals drugs by chemical analysis G01N33/94
• CPC Class Codes: G01N 33/94 involving narcotics or drugs or pharmaceuticals, neurotransmitters or associated receptors

Abstract

Methods and systems for assessing patient compliance with opioid drug therapy are provided. A liquid chromatography tandem mass spectrometer (LC/MS/MS) can be used to simultaneously detect a set of measurements including an amount of at least ten opioids (and their metabolites) in a body fluids sample from a patient. The set of at least ten opioids can include at least oxymorphone and fentanyl. The amounts of opioids and their metabolites are analyzed. For example, the ratios of opioids and their respective metabolites can be used to determine which opioids a patient has been administered. A report of patient compliance is generated based on the set of measurements.

Claims

1. A method for assessing patient compliance with opioid drug therapy, the method comprising:

simultaneously detecting a set of measurements including an amount of at least ten opioids in a body fluids sample from a patient using a liquid chromatography tandem mass spectrometer (LC/MS/MS), wherein the set of at least ten opioids includes at least oxymorphone and fentanyl; and

generating a report of patient compliance based the set of measurements.

2. The method of claim 1, wherein the report of patient compliance comprises ratios of concentrations of opioids and their respective metabolites.

3. The method of claim 2, further comprising determining a set of discrepant and/or consistent results for a plurality of opioids based on a comparison of the set of measurements with data relating to prescription information for the patient.

4. The method of claim 3, wherein the discrepant and consistent results indicate whether a patient is taking opioids being prescribed and/or taking additional drug.

5. The method of claim 1, wherein the set of measurements includes detected threshold amounts of each of said opioids below 10 ng/ml in said sample.

6. The method of claim 1, wherein the set of measurements includes detected threshold amounts of fentanyl and nor-fentanyl as low as 2 ng/ml and detected threshold amounts of oxymorphone, morphine, hydrocodone, hydromorphone, oxycodone, codeine, 6-monoacetylmorphine and meperidine as low as 5 ng/ml in said sample.

7. The method of claim 1, wherein the set of at least ten opioids includes hydrocodone, hydromorphone, oxycodone, oxymorphone, codeine, morphine, 6-monoacetylmorphine, meperidine, fentanyl and nor-fentanyl.

8. The method of claim 1, wherein the set of measurements further includes a detected absence or presence of one or more drugs of abuse.

9. The method of claim 8, wherein the drugs of abuse include alcohol, amphetamines, barbiturates, benzodiazepines, cocaine, marijuana, methadone, phencyclidine and/or propoxyphene.

10. The method of claim 1, wherein generating the report of patient compliance comprises, if the set of measurements indicates a ratio of oxymorphone to oxycodone of greater than 20-30%, generating a notice indicating an oxymorphone source from oxycodone metabolism and/or oxymorphone use.

11. The method of claim 1, wherein generating the report of patient compliance comprises, if the set of measurements indicates a ratio of oxymorphone to oxycodone of less than 20-30%, generating a notice indicating an oxymorphone source from oxycodone metabolism.

12. The method of claim 10, wherein generating the report of patient compliance comprises comparing the oxymorphone source with prescription information indicating whether the patient is prescribed the indicated oxymorphone source, and determining if the patient is compliant or non-compliant based on the comparison.

13. The method of claim 1, further comprising partially purifying the sample using gravity flow solid phase extraction before simultaneously detecting a set of measurements using an LC/MS/MS.

14. The method of claim 13, wherein the steps of partially purifying the sample and simultaneously detecting are performed using an automated robotic workstation.

15. The method of claim 13, wherein the step of partially purifying the sample comprises partially purifying the sample by a process comprising applying a body fluid sample to a cation exchange column, washing the column with an aqueous wash solution, and then eluting the partially purified body fluid sample from the column with an ammoniated organic solvent.

16. The method of claim 1, wherein the body fluid is selected from the group consisting of urine, blood, serum, plasma, saliva, perspiration, meconium, and/or homogenized cord tissue

17. The method of claim 1, one of the at least ten opioids comprises morphine and codeine, and generating a report of patient compliance further comprising:

detecting a negative or positive 6-monoacetylmorphine result as part of the set of measurements;

if 6-monoacetylmorphine is detected and a concentration of codeine is negative, generating a notice indicating a morphine source consistent with heroin use;

if 6-monoacetylmorphine is not detected and a concentration of codeine is negative, generating a notice indicating a morphine source consistent with morphine use;

if 6-monoacetylmorphine is not detected, a concentration of codeine is detected, and a morphine/codeine ratio is less than 55%, generating a notice indicating a morphine source from codeine metabolism;

if 6-monoacetylmorphine is not detected, a concentration of codeine is detected, and a morphine/codeine ratio is greater than 55%, generating a notice indicating a morphine source from codeine metabolism and morphine use; and

if 6-monoacetylmorphine is detected and a concentration of codeine is detected, generating a notice indicating a morphine source from heroin use and codeine metabolism to morphine.

18. The method of claim 1, wherein the set of at least ten opioids includes hydrocodone and codeine, and generating a report further comprises:

if a ratio of hydrocodone to codeine is less than 40%, generating a notice that the hydrocodone source is likely from hydrocodone use and/or high dose codeine metabolism to hydrocodone;

if a ratio of hydrocodone to codeine is greater than 40%, generating a notice that the hydrocodone source is likely from high dose codeine metabolism to hydrocodone and/or hydrocodone use; and

if hydrocodone is detected and codeine is not detected, generating a notice that the hydrocodone source is consistent with hydrocodone use.

19. The method of claim 1, wherein the set of at least ten opioids includes hydromorphone and morphine, and generating a report further comprises:

if a ratio of hydromorphone to morphine is less than 25%, generating a notice that the hydromorphone source is from morphine and/or hydromorphone use; and

if a ratio of hydromorphone to morphine is greater than 25%, generating a notice that the hydromorphone source is from high dose morphine metabolism and/or hydromorphone use.

20. The method of claim 19, wherein the set of at least ten opioids includes hydrocodone, and generating a report further comprises:

if a ratio of hydromorphone to morphine is greater than 25% and a ratio of hydromorphone to hydrocodone is greater than 30%, generating a notice that the hydromorphone source is from hydrocodone metabolism and/or hydromorphone use;

if a ratio of hydromorphone to morphine is greater than 25% and a ratio of hydromorphone to hydrocodone is less than 30%, generating a notice that the hydromorphone source is from hydrocodone metabolism;

if a ratio of hydromorphone to morphine is less than 25% and a ratio of hydromorphone to hydrocodone is greater than 30%, generating a notice that the hydromorphone source is from hydrocodone metabolism and/or hydromorphone use; and

if a ratio of hydromorphone to morphine is less than 25% and a ratio of hydromorphone to hydrocodone is less than 30%, generating a notice that the hydromorphone source is from hydrocodone metabolism and/or high does morphine metabolism.

21. The method of claim 1, one of the at least ten opioids comprises morphine and codeine, and generating a report of patient compliance further comprising:

if a morphine/codeine ratio is less than 55%, generating a notice indicating a morphine source from codeine metabolism; and

if a morphine/codeine ratio is greater than 55%, generating a notice indicating a morphine source from codeine metabolism and morphine use.

22. The method of claim 16, further comprising comparing an indication of opioid source to prescription information to determine if a patient is compliant.

23. A system for assessing patient compliance with opioid drug therapy, the system comprising:

a liquid chromatography tandem mass spectrometer (LC/MS/MS) configured to simultaneously detect a set of measurements including an amount of at least ten opioids (and their metabolites) in a body fluids sample from a patient, wherein the set of at least ten opioids includes at least oxymorphone and fentanyl; and

a module configured to generate a report of patient compliance based the set of measurements.

24. The system of claim 23, wherein the report of patient compliance comprises ratios of concentrations of opioids and their respective metabolites.

25. The system of claim 24, wherein a set of discrepant and/or non-discrepant results for a plurality of opioids is determined by comparing the set of measurements with data relating to prescription information for the patient.

26. The system of claim 25, wherein the discrepant and consistent results indicate whether a patient is taking opioids being prescribed and/or taking additional drug.

27. The system of claim 23, wherein the set of measurements includes detected threshold amounts of each of said opioids below 10 ng/ml in said sample.

28. The system of claim 23, wherein the set of measurements includes detected threshold amounts of fentanyl and nor-fentanyl as low as 2 ng/ml and detected threshold amounts of oxymorphone, morphine, hydrocodone, hydromorphone, oxycodone, codeine, 6-monoacetylmorphine and meperidine as low as 5 ng/ml in said sample.

29. The system of claim 23, wherein the set of at least ten opioids includes hydrocodone, hydromorphone, oxycodone, oxymorphone, codeine, morphine, 6-monoacetylmorphine, meperidine, fentanyl and nor-fentanyl.

30. The system of claim 23, wherein the set of measurements further includes a detected absence or presence of one or more drugs of abuse.

31. The system of claim 30, wherein the drugs of abuse include alcohol, amphetamines, barbiturates, benzodiazepines, cocaine, marijuana, methadone, phencyclidine and/or propoxyphene.

32. The system of claim 23, wherein if the set of measurements indicates a ratio of oxymorphone to oxycodone of greater than 20-30%, the module is configured to generate the report of patient compliance to include a notice indicating an oxymorphone source from oxycodone metabolism and/or oxymorphone use.

33. The system of claim 23, wherein if the set of measurements indicates a ratio of oxymorphone to oxycodone of less than 20-30%, the module is configured to generate the report of patient compliance to include a notice indicating an oxymorphone source from oxycodone metabolism.

34. The system of claim 32, wherein the module is further configured to generate the report of patient compliance by comparing the oxymorphone source with prescription information indicating whether the patient is prescribed the indicated oxymorphone source, and determining if the patient is compliant or non-compliant based on the comparison.

35. A method for assessing opioid drug source, the method comprising:

simultaneously detecting a set of measurements including an amount of at least ten opioids in a body fluids sample from a subject using a liquid chromatography tandem mass spectrometer (LC/MS/MS), wherein the set of at least ten opioids includes at least oxymorphone and fentanyl; and

generating a report of potential opioid source(s) based on the set of measurements.

36. The method of claim 35, wherein the simultaneously detecting is performed before prescribing an opioid to a subject.

37. The method of claim 35, wherein generating a report comprises assessing patient compliance with known prescription information.

38. The method of claim 35, wherein the sample comprises a forensic sample.

39. The method of claim 35, wherein the report of potential opioid source(s) comprises ratios of concentrations of opioids and their respective metabolites.

40. The method of claim 39, further comprising identifying the potential opioid source(s) using the ratios of concentrations of opioids and their respective metabolites

41. A system for assessing patient compliance with opioid drug therapy, the system comprising:

a liquid chromatography tandem mass spectrometer (LC/MS/MS) configured to simultaneously detect a set of measurements including an amount of a plurality of opioids (and their metabolites) in a body fluids sample from a patient, wherein the plurality of opioids includes at least oxymorphone and fentanyl and the body fluids sample is provided with machine-readable codes configured to identify prescription information corresponding to the patient;

a report generation module in communication with the LC/MS/MS;

a prescription reader in communication with the report generation module, wherein the prescription reader is configured to automatically receive the machine-readable codes and to input the codes to the report generation module,

wherein the report generation module is configured to generate a report of patient compliance based the set of measurements and the prescription information provided by the machine-readable codes.

42. The system of claim 41, wherein the codes are barcodes.