Morphine

Common/Brand Names
Avinza, Kadian, MS Contin, DepoDur, Embeda, MSIR, Oramorph SR, Duramorph, Roxanol
Expected Screen Results
Opiates
Expected Confirmation Results
Morphine / Hydromorphone
Confirmation Cutoff
20
ng/mL
Detection Time
Up to
3
Days
Notes
Morphine is sold as a drug and the metabolite of codeine and heroin, a positive result may also be due to poppy seed ingestion
drug image

INTRODUCTION

Morphine is a Schedule II drug that exists as a natural alkaloid in the plant Papaver somniferum and is prescribed under the following trade names: Astramorph, Avinza, DepoDur, Duramorph, Kadian, Kapanol, MS Contin, MSIR, Oramorph and Roxanol 1,2. Morphine is a µ receptor agonist, which causes a reduction in asyclic adenosine monophosphate, an increase of intracellular potassium concentration, and cell membrane hyperpolarization3. Continued use may lead to tolerance and addiction2,3.

PHARMACOLOGY

ADMINISTRATION:

Morphine is administered subcutaneously, intramuscularly, intravenously, or as an intrathecal injection with a typical dose of 1-10 mg/kg; however it can also be administered orally with a typical dose of 2-200 mg2. 

DISTRIBUTION:

Morphine is highly distributed throughout the body; however due to first-pass metabolism, only 20-40% is bioavailable3. The half-life of morphine is 1.3 - 6.7 hours with the peak serum concentration averaging around 0.8-1.6 hours for a single 30 mg oral dose2. 

METABOLISM:

Morphine is primarily metabolized by glucurindation as well as N-dealkylation to form pharmacologically inactive morphine-3-glucuronide (M3G), pharmacologically active morphine-6-glucuronide (M6G), and normorphine, respectively. Additionally, a minor metabolite, hydromorphone may be present in chronic pain management patients prescribed morphine. Morphine is also a metabolite of codeine, ethylmorphine, heroin and pholcodine.

EXCRETION:

Morphine is largely excreted through the bile with significant enterohepatic circulation of morphine and its metabolites. Up to 87% of the dose is excreted in urine as conjugates, with 75% present as M3G, within 72 hours. Additionally, a small percentage of the drug conjugate is excreted through the feces2. 

METHODS OF ANALYSIS

The opiate screening methodology utilized for the detection of morphine and metabolites is the Enzyme Immunoassay (EIA) with a cutoff concentration of 300 ng/mL. Qualitative and quantitative confirmation is performed by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) with at the cutoff concentration of 20 ng/mL. The urine samples are hydrolyzed prior to analyses and total morphine (morphine, M3G, M6G) concentration is reported.

INTERPRETATION

Morphine lacks major metabolites other than the glucuronides; therefore, typically only morphine should be present in urine from patients prescribed this drug. In chronic pain management patients, it is possible to detect the minor metabolite hydromorphone5. In a study completed by Heltsley et al. a total of 2704 patients were positive for morphine and out of these 333 specimens contained hydromorphone (12.3%)6.

Interpretations of drug analysis reports should be conducted with caution and utilize the complete medical history of the patient.  6-Acetylmorphine (6-AM) is a metabolite of heroin and rapidly metabolizes to morphine.  Morphine is also a metabolite of codeine and can account for 15% of codeine metabolites excreted in urine. Typically, codeine is present at a higher concentration than morphine2. Additionally, the ingestion of poppy seeds may cause a positive morphine, but morphine concentrations are usually below 1000 ng/mL7.

References
  1. Goldberger, B. A. Quantitation of Opioids in Blood and Urine Using Gas Chromatography-Mass Spectrometry (GC-MS). In, Garg, U, Hammett-Stabler, C.A, editiors. Clinical Applications of Mass Spectrometry Methods and Protocols. New York, NY: Humana Press, 2009;399-410.
  2. Baselt, R. C. Disposition of Toxic Drugs and Chemicals in Man 9th ed. Seal Beach, California: Biomedical Publications. 2011.
  3. Stout, P. R. Opiods. In Ropero-Miller J. D., Goldberger B.A, editors.Handbook of Workplace Drug Testing 2nd ed  Washington, D.C.: AACC Press. 2009;289-316.
  4. Mitchell, J. M., Paul B.D., Welch, P., Cone E.J., Forensic Drug Testing for Opiates. II. Metabolism and    Excretion Rate of Morphine In Humans After Morphine Administration. Journal of Analytical Toxicology. 1991 March/April; 15:49-53.
  5. Cone E.J, Heit H.A, Caplan Y.H, Gourlay, D., Evidence of Morphine Metabolism to Hydromorphone in Pain Patients Chronically Treated with Morphine. Journal of Analytical Toxicology. 2006 January/February; 30:1-5
  6. Heltsley, R., Zichterman, A., Black, D.L., Cawthon, B., Robert, T., Moser,F., Caplan, Y.H., Cone, E.J. Urine Drug Testing of Chronic Pain Patients. II. Prevalance Patters of Prescription Opiates and Metabolites. Journal of Analytical Toxicology. 2010. January/February;34:32-38
  7. Rohrig, T. P.Moore, C., The Determination of Morphine in Urine and Oral Fluid Following Ingestion of Poppy Seeds. Journal of Analytical Toxicology.2003 October; 27:450-450.