Fentanyl / Norfentanyl

Common/Brand Names
Duragesic, Actiq, Sublimaze
Expected Screen Results
Fentanyl
Expected Confirmation Results
Fentanyl / Norfentanyl
Confirmation Cutoff
2
ng/mL
Detection Time
Up to
3
Days
Notes
Synthetic narcotic analgesic of high potency and short duration of action
drug image

INTRODUCTION

Fentanyl, a Schedule II synthetic opiate, belongs to the phenylpiperidine group1. This drug is a µ-receptor agonist analgesic that is 50-100 times more potent than morphine and has a short duration of action1,2. It is prescribed for moderate to severe pain under the following trade names: Abstral, Actiq, Duragesic, Fentora, Lazanda, Sublimaze, and Sybsys. Fentanyl is widely prescribed with 6.9 million prescriptions being dispensed in 2012 and 3.4 million in the first half of 20133. 

PHARMACOLOGY                                            

ADMINISTRATION:

Fentanyl is administered in a variety of different ways. These methods range in concentration and invasiveness from parenteral injection to a transmucosal lozenge/sublingual spray with a typical dose of 0.05 mg and 0.2 – 1.6 mg, respectively. Fentanyl can also be administered orally via a buccal film or a sublingual film/tablet with a typical dose of 0.1-0.8 mg. Additionally, an extended-release formulation with a dose of 12.5-100 µg/hr is available via a transdermal patch2. 

DISTRIBUTION:

Fentanyl is readily absorbed by the body although the administration and the potency have the potential of effecting the distribution. Following a single 0.8 mg transmucosal dose, average peak plasma concentration occurred at 0.8 hours with a half-life of 3-12 hours. Following an application of a 25 µg/hr transdermal patch, average serum concentrations ranged from 0.3-1.2 µg/L within 24 hours with a half-life of 17 hours upon the removal of the patch2. Transmucosal administration has a 50% bioavailability of the total concentration of drug per dose whereas a transdermal patch will continue to release a set concentration of drug in several doses over a number of hours5.

METABOLISM:
Fentanyl is primarily metabolized in the liver into the inactive metabolite norfentanyl. Specifically, fentanyl undergoes N-dealkylation catalyzed by the CYP3A4 enzyme2-4.
EXCRETION:

Fentanyl is normally excreted quickly from the body after ingestion. A human body typically requires 3-4 days in order to excrete approximately 85% of the dose in urine with 0.4-6% and 26-55% as parent drug and norfentanyl, respectively. A small percentage of the urine will include other metabolites formed through smaller metabolic pathways in the excretory process2. 

 

Methods of Analysis

A highly selective and specific fentanyl Enzyme Immunoassay screening methodology is utilized for the detection of fentanyl with a cutoff concentration of 2 ng/mL. The presence of both fentanyl and its primary metabolite norfentanyl, can be confirmed and quantified using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) with a cutoff concentration of 2 ng/mL.

INTERPRETATION

Patients prescribed fentanyl should contain both fentanyl and norfentanyl in the urine. Since each individual physiology is unique, interpretations of the drug analysis reports should be conducted with caution utilizing all available resources including the complete medical history of the patients. If fentanyl is present with high concentrations in the urine without any accompanying norfentanyl, the possibility of patient tampering should be considered. However, patients co-administered CYP3A4 inhibitors may have lower than expected concentrations of norfentanyl. It may also be important to consider the administration method when interpreting results. In a study conducted by Poklis and Backer, norfentanyl concentrations were found to be 3-4 times greater than that of fentanyl, on average, in patients administered the Duragesic® transdermal patch6. 

References

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.Baselt, R. C. (2011) Disposition of Toxic Drugs and Chemicals in Man, 9th Edition. Biomedical Publications, Seal Beach, CA, 675-678.Drug Enforcement Administration. (2013) Fentanyl. Retrieved from deadivision.gov. http://www.deadiversion.usdoj.gov/drug_chem_info/fentanyl.pdf.Food and Drug Administration (2003) Duragesic® Fentanyl Transdermal System CII Retrieved from FDA.Gov http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/19813s39lbl.pdf.Physicians’ Desk Reference. (2007). Thomson PDR, Monvale, New Jersey.Poklis, A., Backer, R., (2004) Urine Concentrations of Fentanyl and Norfentanyl During Application of Duragesic® Transdermal Patches.Journal of Analytical Toxicology, 28, 422-425