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Interpretive Handbook

Test 83132 :
Morphine, Unconjugated, Serum

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Morphine interacts primarily with mu-opioid receptor to mediate its effects, but also shows some affinity for kappa-opioid receptor.(1) Its major metabolites are glucuronide conjugates including: inactive morphine-3-glucuronide (M3G, approximately 60%), active morphine-6-glucuronide (M6G, approximately 10%), and a small amount of morphine-3,6-diglucuronide.(2,3)  The enzyme UDP-glucuronosyltransferase-2B7 (UGT2B7) is primarily responsible for morphine glucuronidation.(2)

Useful For Suggests clinical disorders or settings where the test may be helpful

Monitoring morphine therapy


Routine drug monitoring is not indicated in all patients. Compliance monitoring is indicated in patients who are being treated for acute pain requiring excessive dose.


Assessing toxicity

Interpretation Provides information to assist in interpretation of the test results

The minimal effective peak serum concentration of unconjugated morphine for analgesia is 20 ng/mL. Peak therapeutic serum concentrations of 70 to 450 ng/mL occur 30 minutes after intravenous dose, 1 hour after intramuscular or subcutaneous dose, or 2 hours after oral dose.


Patients continuously administered morphine develop tolerance; they can tolerate serum concentrations up to 1,500 ng/mL.


Death may be associated with serum total morphine >700 ng/mL in the nontolerant subject.(4)

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

This test quantifies unconjugated morphine. This test does not quantify morphine-3-glucuronide and morphine-6-glucuronide. This test cannot distinguish the source of morphine from heroin, codeine, or prescription morphine.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

Therapeutic: 70-450 ng/mL

Tolerant patients: <1,500 ng/mL

Toxicity: >700 ng/mL

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Gutstein HB, Akil H: Opioid analgesics. In Goodman and Gilman's The Pharmacological Basis of Therapeutics. 11th edition. Edited by LL Brunton, JS Lazo, KL Parker. New York, McGraw-Hill Book Company, 2006, pp 547-590; available from URL: http://www.accessmedicine.com/content.aspx?aID=940653

2. Coffman BL, Rios GR, King CD, et al: Human UGT2B7 catalyzes morphine glucuronidation. Drug Metab Dispos 1997;25:1-4

3. Wittwer E, Kern SE: Role of morphine's metabolites in analgesia: concepts and controversies. AAPS J 2006 May 26;8(2):E348-352

4. Baselt RC: Morphine. In Disposition of Toxic Drugs and Chemical in Man. Eighth edition. Edited by RC Baselt, Foster City, CA, Biomedical Publications, 2008, pp 1057-1061