Open Access Open Access  Restricted Access Subscription or Fee Access

Quantification of oxycodone and morphine analytes in urine: Assessment of adherence

Michael E. M. Larson, PhD, Richard L. Berg, MS, Joyce Flanagan, PhD


Objective: To use urine drug testing (UDT) results and other covariates to develop a model for the assessment of opioid medication prescription adherence.

Design: Retrospective study.

Setting: The Pain Management Clinic at one center of a large, private, multispecialty healthcare system (consisting of 52 regional centers) in northcentral and western Wisconsin.

Participants: Seven hundred thirty-three Pain Management Clinic patients with an opioid prescription and UDT between June 1, 2007 and May 17, 2010. UDT results were available for 2,615 individual drug screens from 2,364 urine samples.

Intervention: Patient characteristics, drug dosage, quantitative urine creatinine and drug/analyte levels, and reported adherence/nonadherence were abstracted from the electronic medical record.

Main outcome measures: Adherence was categorized for all UDT results using an objective set of criteria. Drug adherence was modeled excluding samples for clinically observed adherence issues, detection of illicit substances, diagnosed addictive disorders, and/or metabolic reasons.

Results: Considerable variability was observed for primary urine analytes, even among those prescribed the same dose and believed to be adherent and free of confounding medical issues. For all medications evaluated, only urine creatinine contributed significantly (p < 0.0001) to predictive models of adherence based on dose alone. Simulated underuse and review of identified overuse and underuse suggest that this model could provide useful adherence information.

Conclusion: Predictive models based on urine analyte levels and clinical covariates, particularly urine creatinine, may be clinically useful for assessing opioid adherence. Future work should evaluate whether genetics or other factors can improve predictive accuracy of these models.


chronic pain, creatinine, drug abuse, oxycodone, OxyContin, morphine, Kadian, urine specimen, urine drug testing

Full Text:



Okie S: A flood of opioids, a rising tide of deaths. N Engl J Med. 2010; 361(21): 1981-1985.

Christo PJ, Manchikanti L, Ruan X, et al.: Urine drug testing in chronic pain. Pain Physician. 2011; 14(2): 123-143.

Gilbert JW, Wheeler GR, Mick GE, et al.: Urine drug testing in the treatment of chronic noncancer pain in a Kentucky private neuroscience practice: The potential effect of Medicare benefit changes in Kentucky. Pain Physician. 2010; 13(2): 187-194.

Nafziger AN, Bertino JS Jr: Utility and application of urine drug testing in chronic pain management with opioids. Clin J Pain. 2009; 25(1): 73-79.

Katz NP, Sherburne S, Beach M, et al.: Behavioral monitoring and urine toxicology testing in patients receiving long-term opioid therapy. Anesth Analg. 2003; 97(4): 1097-1102.

Gourlay D, Heit HA: The art and science of urine drug testing. Clin J Pain. 2010; 26(4): 358.

Larson ME, Richards TM: Quantification of a methadone metabolite (EDDP) in urine: Assessment of compliance. Clin Med Res. 2009; 7(4): 134-141.

Cuoto JE, Webster L, Romney MC, et al.: Using an algorithm applied to urine drug screening to assess adherence to a hydrocodone regimen. J Clin Pharm Ther. 2010; 36(2): 200-207.

Pesce A, Crews B, Latyshev S, et al.: Improvement of pain physicians’ practices of opioid management: Population-based urinary excretion data. J Opioid Manag. 2011; 7(6): 435-441.

Pesce A, West C, West R, et al.: Determination of medication cutoff values in a pain patient population. J Opioid Manag. 2011; 7(2): 117-122.

Yee DA, Best BM, Atayee RS, et al.: Observations on the urine metabolic ratio of oxymorphone to oxycodone in pain patients. J Anal Toxicol. 2012; 36(4): 232-238.

Bell R, Taylor EH, Ackerman B, et al.: Interpretation of urine quantitative 11-nor-delta-9 tetrahydrocannabinal-9-carboxylic acid to determine abstinence form marijuana smoking. J Toxicol Clin Toxicol. 1989; 27(1-2): 109-115.

Fraser AD, Worth D: Urinary excretion profiles of 11-nor-9-carboxy-delta9-tetrahydrocannabinol: A delta9-THC-COOH to creatinine ratio study #2. Forensic Sci Int. 2003; 133(1-2): 26-31.

Lafolie P, Beck O, Hjemdahl P, et al.: Using relation between urinary cannabinoid and creatinine excretions to improve monitoring of abuser adherence to abstinence. Clin Chem. 1994; 40(1): 170-171.

Lafolie O, Beck O, Blennow G, et al.: Importance of creatinine analyses of urine when screen for abused drugs. Clin Chem. 1999; 37(11): 1927-1931.

Levey AS, Coresh J, Greene T, et al.: Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006; 145(4): 247-254.

Wu Chen NB, Schaffer MI, Lin RL, et al.: Simultaneous quantitation of morphine and codeine in biological samples by electron impact mass fragmentography. J Anal Toxicol. 1982; 6(5): 231-234.

Grinstead GF: A closer look at acetyl and pentafluoropropionyl derivatives for quantitative analysis of morphine and codeine by gas chromatography/mass spectrometry. J Anal Toxicol. 1991; 15(6): 293-298.

Jennrich RI, Schluchter MD: Unbalanced repeated-measures models with structured covariance matrices. Biometrics. 1986; 42(4): 805-820.

Littell RC, Milliken GA, Stroup WW, et al.: SAS® for Mixed Models. Cary, NC: SAS Institute Inc., 2006.



  • There are currently no refbacks.