Method and device for monitoring medication usage

Abstract

The present invention provides methods for detecting and quantifying metabolites in a biological sample by measuring the concentration of a test metabolite in the sample and comparing that concentration against the concentration of the reference metabolite; enabling accurate metabolite concentration measurements to determine aberrant drug usage patterns. Also disclosed is an analytical testing device and related computer-assisted products for detecting and quantifying metabolites in a biological sample efficiently and accurately.

We claim: 
     
         1 . A method of determining a drug dose taken by a subject, the method comprising:
 (a) determining a concentration of a test metabolite and a reference metabolite in a biological sample obtained from a subject, wherein the test metabolite is the drug or a metabolite of the drug;   (b) determining the normalized concentration of the test metabolite in the biological sample as a ratio of the concentration of the test metabolite to the concentration of the reference metabolite; and   (c) determining the drug dose taken by the subject by using a database to determine the drug dose that is correlated with the normalized concentration of the test metabolite obtained in step (b), wherein the database comprises (i) dose of the drug taken by a reference population; (ii) reference metabolite concentration in a medium of biological sampling obtained from the reference population, and (iii) test metabolite concentration in the medium of biological sampling obtained from the reference population.   
     
     
         2 . The method of  claim 1 , wherein the biological sample and the medium of biological sampling are selected from the group consisting of: urine, blood, saliva, sweat, spinal fluid, brain fluid, and combinations thereof. 
     
     
         3 . The method of  claim 1 , wherein the reference metabolite is creatinine. 
     
     
         4 . The method of  claim 1 , wherein concentration of the reference metabolite is determined by contacting the biological sample with a device capable of distinguishing between the test metabolite and the reference metabolite. 
     
     
         5 . The method of  claim 5 , wherein concentration of the reference metabolite is determined using gas chromatography, tandem gas chromatography-mass spectroscopy, or a test strip. 
     
     
         6 . The method of  claim 1 , wherein prior to step (a), the subject has been prescribed a drug therapy regimen, drug dosing therapy, medication regimen, or has been enrolled in a drug treatment program. 
     
     
         7 . The method of  claim 1 , wherein the database is used to develop a regression model correlating a given drug dosage with the other variables included in the database, and wherein step (c) is performed using the regression model. 
     
     
         8 . The method of  claim 7 , wherein the regression model defines one or more dosage-specific confidence intervals. 
     
     
         9 . The method of  claim 1 , further comprising monitoring the subject for possible non-adherence to a prescribed medication regimen by comparing the determined drug dose to the dosage of the drug that is prescribed for the subject. 
     
     
         10 . An interindividual method of determining a drug dose taken by a subject, the method comprising:
 determining a concentration of a test metabolite and a concentration of a reference metabolite in a biological sample obtained from a subject, wherein the test metabolite is the drug or a metabolite of the drug;   determining a normalized concentration of the test metabolite in the biological sample as a ratio of the concentration of the test metabolite to the concentration of the reference metabolite; and   using the normalized concentration of the test metabolite to determine the drug dose taken by the subject, without accounting for any variations between individuals other than reference metabolite concentration.   
     
     
         11 . The method of  claim 10 , wherein the biological sample is urine and the reference metabolite is creatinine. 
     
     
         12 . The method of  claim 10 , wherein the drug is selected from the group consisting of opioids, stimulants, benzodiazepines, and combinations thereof. 
     
     
         13 . The method of  claim 10 , wherein the drug is selected from the group consisting of oxycodone, morphine, codeine, methadone, fentanyl, propoxyphene, hydrocodone, methylphenidate, dextroamphetamine, diazepam, temazepam, alprazolam, lorazepam, buprenorphine, and combinations thereof. 
     
     
         14 . The method of  claim 10 , wherein the test metabolite is selected from the group consisting of a drug, an opioid, a stimulant, a benzodiazepine, oxycodone, morphine, codeine, methadone, fentanyl, propoxyphene, hydrocodone, methylphenidate, dextroamphetamine, diazepam, temazepam, alprazolam, lorazepam, buprenorphine, metabolites thereof, and combinations thereof. 
     
     
         15 . The method of  claim 10 , wherein the concentration of the reference metabolite is determined by contacting the biological sample with a device capable of distinguishing between the test metabolite and the reference metabolite. 
     
     
         16 . The method of  claim 10 , whereby the step of determining the normalized concentration of the test metabolite in the biological sample adjusts the concentration for changes in the subject's hydration status. 
     
     
         17 . A method of monitoring possible non-adherence to a prescribed medication regimen comprising the steps of:
 (a) determining a concentration of a reference metabolite and a concentration of a test metabolite in a biological sample from a patient receiving a prescribed medication regimen;   (b) determining a normalized test metabolite concentration that is adjusted for changes in hydration status of the patient as a ratio of the test metabolite concentration to reference metabolite concentration in the biological sample;   (c) using a database to determine a test metabolite/reference metabolite ratio that is correlated with the prescription medication dosage of the prescribed medication regimen, wherein the database comprises (i) prescription medication dosage administered to a reference population that is receiving the prescribed medication regimen; (ii) test metabolite concentration specific to a medium of biological sampling of the reference population, and (iii) reference metabolite concentration specific to a medium of biological sampling of the reference population,   wherein a mismatch between the test metabolite/reference metabolite ratio that is correlated with the prescription medication dosage of the prescribed medication regimen as determined in step (c) and the normalized test metabolite concentration determined in step (b) indicates non-adherence to the prescribed medication regimen.   
     
     
         18 . The method of  claim 17 , wherein the biological sample and the medium of biological sampling of the reference population are both urine, and the reference metabolite is creatinine. 
     
     
         19 . The method of  claim 18 , wherein the database is used to develop a regression model correlating a given drug dosage with the other variables included in the database, and wherein step (c) is performed using the regression model. 
     
     
         20 . The method of  claim 19 , wherein the regression model defines one or more dosage-specific confidence intervals.