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Epic Code LAB848 Fentanyl, Serum

Important Note

Order as Reference Miscellaneous #LAB848; indicate complete test name when ordering.

Additional Codes

Mayo Code: FENTS

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Useful For

Monitoring fentanyl therapy

Specimen Type

Serum Red

Specimen Required

Collection Container/Tube: Red top (Serum gel/SST are not acceptable)

Submission Container/Tube: Plastic vial

Specimen Volume: 2.3 mL

Collection Instructions: Centrifuge and aliquot serum into plastic vial within 2 hours of collection.

Laboratory Test Directory Note:

COLLECTION NOTE: Volumes listed are in serum or plasma, draw approximately 2 1/2 times the requested volume in whole blood.

Specimen Minimum Volume

1.25 mL


If not ordering electronically, complete, print, and send a Therapeutics Test Request (T831) with the specimen.

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Red Frozen (preferred) 28 days
  Refrigerated  14 days
  Ambient  72 hours

Reject Due To

Gross hemolysis OK
Gross lipemia OK
Gross icterus OK


Specimens collected in serum gel tubes are not acceptable becuase the drug can absorb on the gel and lead to falsely decreased concentrations.

Clinical Information

Fentanyl is an extremely fast acting synthetic opioid related to the phenylpiperidines.(1,2) It is available in injectable as well as transdermal formulations.(1) The analgesic effects of fentanyl is similar to those of morphine and other opioids(1): it interacts predominantly with the opioid mu-receptor. These mu-binding sites are discretely distributed in the human brain, spinal cord, and other tissues.(1,3)


Fentanyl is approximately 80% to 85% protein bound.(1) Fentanyl plasma protein binding capacity decreases with increasing ionization of the drug. Alterations in pH may affect its distribution between plasma and the central nervous system (CNS). The average volume of distribution for fentanyl is 6 L/kg (range 3-8).(3,4)


In humans, the drug appears to be metabolized primarily by oxidative N-dealkylation to norfentanyl and other inactive metabolites that do not contribute materially to the observed activity of the drug. Within 72 hours of intravenous (IV) administration, approximately 75% of the dose is excreted in urine, mostly as metabolites with less than 10% representing unchanged drug.(3,4)


The mean elimination half-life is:(1-3)

-IV: 2 to 4 hours

-Iontophoretic transdermal system (Ionsys), terminal half-life: 16 hours

-Transdermal patch: 17 hours (range 13-22 hours, half-life is influenced by absorption rate)


-Lozenge: 7 hours

-Buccal tablet

-100 to 200 mcg: 3 to 4 hours

-400 to 800 mcg: 11 to 12 hours


In clinical settings, fentanyl exerts its principal pharmacologic effects on the CNS. In addition to analgesia, alterations in mood (euphoria, dysphoria) and drowsiness commonly occur.(1,3) Because the biological effects of fentanyl are similar to those of heroin and other opioids, fentanyl has become a popular drug of abuse.

Method Name

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

Report Available

2 to 7 days

Reporting Name

Fentanyl and Metabolites, S

Reference Values

Not applicable


Both fentanyl and norfentanyl are reported.


Tolerant individuals may require many-fold increases in dose to achieve the same level of analgesia, which can greatly complicate interpretation of therapeutic drug monitoring results and establishment of a therapeutic window.


Concentration at which toxicity occurs varies and should be interpreted in light of clinical situation.

Method Description

Fentanyl is isolated from serum using a liquid/liquid extraction. The solvent is dried and the analytes are reconstituted with mobile phase. Analysis is performed by liquid chromatography-tandemmass spectrometry using selected ion monitoring.(Unpublished Mayo method)

Day(s) Performed

Monday, Wednesday

Clinical Reference

1. Gutstein HB, Akil H: Opioid analgesics. In: Brunton LL, Lazo JS, Parker KL, eds. Goodman and Gilman's: The Pharmacological Basis of Therapeutics. Vol 11. McGraw-Hill Companies; 2006:chap 21

2. Kerrigan S, Goldberger BA: Opioids. In: Levine B, eds. Principles of Forensic Toxicology. 2nd ed. AACC Press; 2003:187-205

3. DURAGESIC (fentanyl transdermal system). Package insert: Janssen Pharmaceutica Products, LP; 2006

4. Baselt RC: Disposition of Toxic Drugs and Chemicals in Man. 10th ed. Biomedical Publications; 2014

Test Classification

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information


G0480 (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
FENTS Fentanyl and Metabolites, S 81275-0


Result ID Test Result Name Result LOINC Value
31829 Norfentanyl 11074-2
31830 Fentanyl 3636-8
31832 Chain of Custody 77202-0