Oxycodone / Noroxycodone

Common/Brand Names
Endocet, OxyContin, Percocet, Percodan, Roxicodone
Expected Screen Results
Opiates
Expected Confirmation Results
Oxycodone / Oxymorphone / Noroxycodone / Noroxymorphone
Confirmation Cutoff
20
ng/mL
Detection Time
Up to
3
Days
Notes
Some preliminary screens may be positive for oxycodone and opiates. Metabolized by CYP isoenzymes. A positive oxycodone and negative oxymorphone could be due to inter-individual metabolism of oxymorphone
drug image

INTRODUCTION

Oxycodone is a Schedule II semi-synthetic opiate derived from thebaine and is part of the phenanthrenes group that is based off the morphine structure1. Additionally, this drug is a µ receptor agonist2. It is prescribed under the following trade names: Oxycontin, Oxycet, Roxicodone, Endocet, Endodan, Percocet, Percodan, and Roxicet. Oxycodone is prescribed as a narcotic analgesic for moderate to moderately severe pain. 

PHARMACOLOGY                                            

ADMINISTRATION:

Oxycodone is administered orally via a solution, tablet or capsule with typical doses of 5-100 mg/5 mL or 2.5-30 mg, respectively. Additionally, an extended release formulation with a dose of 10-80 mg is available. Frequently, drugs such as acetaminophen, aspirin, or ibuprofen are present in the medication4. 

DISTRIBUTION:

Following a 10 mg oral dose of oxycodone, peak serum concentrations occurred around 0.8-2.5 hours with a half-life of 3-6 hours4. Oxycodone has a high bioavailability of up to 60%2.

METABOLISM:

Oxycodone is metabolized extensively in the liver by demethylation at the O and the N positions in order to form oxymorphone (OM) and noroxycodone (NOC), respectively2,4. Oxycodone is metabolized through the CYP2D6 enzyme to produce the pharmacologically active metabolite OM. Due to a genetic polymorphism of CYP2D6, this metabolic pathway may have reduced metabolism, which may adversely affects the therapeutic efficacy5. Pharmacologically inactive NOC is metabolized by CYP3A4 and is unaffected by the CYP2D6 polymorphism.

EXCRETION:

The majority of the parent drug and metabolites are excreted over a phase of 36 hours, with approximately 72% being present in the 48 hour urine4,6.

METHODS OF ANALYSIS

Oxycodone demonstrates poor cross-reactivity with the opiate assay; therefore, the highly specific oxycodone screening Enzyme Immunoassay (EIA) methodology is utilized for the detection of oxycodone with a cutoff concentration of 300 ng/mL . Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) is used to confirm and quantify oxycodone, with a cutoff concentration at 20 ng/mL. Subsequent to analyses, the urine concentrations of oxycodone and its two primary metabolites are reported.

INTERPRETATION

For patients regularly prescribed oxycodone, the parent drug along with the metabolites should be detected in the urine. In a study conducted by Heltsely, et al., of 5046 specimens analyzed for oxycodone, 65.3% contained both oxycodone and metabolites, 14.9% contained only metabolites of oxycodone and 4.0% contained only parent drug7. If only oxycodone is present in high concentrations, the possibility of patient tampering should be considered.

The interpretation of patients prescribed oxycodone should be conducted with caution since OM is also prescribed and/or abused. NOC is metabolized directly from oxycodone and has a longer detection time; therefore it may assist with interpretation8. Additionally, oxycodone preparation may contain hydrocodone as an impurity up to 0.12% and oxycodone is a known impurity in oxymorphone preparations up to 0.4%9.

References
  1. Ropero-Miller. J.D., Goldberger.B.A (2001) Opioids. In Shaw.L.M. (eds). The Clinical Toxicology Laboratory Contemporary Practice of Poisoning Evaluation, Chapter 6. AACC Press. Washington, D.C., 73-95.
  2. Stout, P. R.  (2009) Opioids. In Ropero-Miller J. D., Goldberger B.A. (eds.) Handbook of Workplace Drug Testing 2nd edition, Chapter 10.  AACC Press. Washington, D.C., 289-316.
  3. Purdue Pharma LP, (2014) Oxycotin-Oxycodone Hydrochloride tablet, film coated, extended release. Retrieved from purduepharma.com. http://app.purduepharma.com/xmlpublishing/pi.aspx?id=o.
  4. Baselt, R. C. (2011) Disposition of Toxic Drugs and Chemicals in Man, 9th Edition. Biomedical Publications, Seal Beach, CA, 1259-1262.
  5. Mikus. G., Weiss. J. (2005) Influence of CYP2D6 Genetics on Opioid Kinetic, Metabolism and Response. Current Pharmacogenomics3, 43-52.
  6. Lalovic, B., Kharash, E., Hoffer, C., Risler, L., Liu-Chen, L.Y., Shen, D.D., (2006) Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: Role of circulating active metabolites. Clinical Pharmacology & Therapeutics78 (5), 461-479.
  7. Heltsley, R., Zichterman, A., Black, D.L., Cawthon, B., Robert, T., Moser,F., et al. (2010) Urine Drug Testing of Chronic Pain Patients. II. Prevalence Patters of Prescription Opiates and Metabolites. Journal of Analytical Toxicology, 34, 32-38.
  8. Elder, N.M., Atayee, R.S., Ma, J.D., (2014) Observations of Urinary Oxycodone and Metabolite Distributions in Pain Patients. Journal of Analytical Toxicology, 38, 129-134.
  9.  American Association of Medical Review Officers. (2010) Interpreting Test Results for Prescription Opiates. MRO Alert,3, 1-3.