Fentanyl
[CAS# 201415-26-1]

Identification

• Classification: Organic raw materials >> Heterocyclic compound >> Piperidines
• Name: Fentanyl
• Synonyms: N-phenyl-N-[1-(2-phenylethyl)piperidin-4-yl]propanamide
• Molecular Formula: C₂₂H₂₈N₂O
• Molecular Weight: 336.47
• CAS Registry Number: 201415-26-1
• EC Number: 207-113-6
• SMILES: CCC(=O)N(C1CCN(CC1)CCC2=CC=CC=C2)C3=CC=CC=C3

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Melting point: 82 - 84 ºC (Expl.)
• Boiling point: 466.2±38.0 ºC 760 mmHg (Calc.)^*
• Flash point: 185.8±19.1 ºC (Calc.)^*
• Solubility: Soluble 40 mM (water) (Expl.)
• Index of refraction: 1.585 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS06;GHS07;GHS08 Danger
• Hazard Statements: H300-H310-H317-H330-H334-H361-H362-H413
• Precautionary Statements: P203-P233-P260-P261-P262-P263-P264-P270-P271-P272-P273-P280-P284-P301+P316-P302+P352-P304+P340-P316-P318-P320-P321-P330-P333+P317-P342+P316-P361+P364-P362+P364-P403-P403+P233-P405-P501

Discovory and Applicatios

Fentanyl is a synthetic opioid analgesic that exhibits potent activity as an agonist at the μ-opioid receptor. It was first synthesized in the early 1960s as part of efforts to develop new anesthetic agents with strong analgesic properties and rapid onset of action. The compound is structurally related to phenylpiperidines and is characterized by high lipid solubility, which facilitates its rapid penetration into the central nervous system. Clinically, fentanyl is used for the management of severe pain, including perioperative analgesia and treatment of chronic pain in cancer patients.

Pharmacologically, fentanyl exerts its effects by binding to μ-opioid receptors located in the brain and spinal cord, leading to inhibition of neurotransmitter release and attenuation of pain signaling. Its potency is estimated to be approximately 50 to 100 times greater than morphine. This high efficacy allows for the administration of fentanyl at very low doses, particularly in the form of transdermal patches, sublingual tablets, nasal sprays, and intravenous injections.

The synthesis of fentanyl involves a multi-step process that typically begins with the preparation of a substituted aniline derivative. This is followed by the formation of a 4-anilidopiperidine structure through amide bond formation and further modification of the piperidine ring. Structural analogs of fentanyl have been developed to optimize pharmacokinetics and receptor selectivity, leading to derivatives such as sufentanil, alfentanil, and remifentanil, each with specific clinical applications.

While fentanyl's clinical utility is well established, its high potency and narrow therapeutic index have also contributed to its involvement in opioid misuse and overdose incidents. Illicitly manufactured fentanyl and its analogs have become a significant contributor to opioid-related fatalities in many regions. These non-pharmaceutical variants are often distributed in powder form or mixed with other drugs, leading to unpredictable potency and increased risk of respiratory depression and death.

Fentanyl undergoes hepatic metabolism primarily via cytochrome P450 3A4-mediated N-dealkylation to produce norfentanyl, an inactive metabolite. The drug and its metabolites are excreted in urine, and their detection in biological specimens is a key indicator of exposure. Analytical methods such as liquid chromatography coupled with tandem mass spectrometry are commonly used for the quantification of fentanyl and its metabolites in clinical and forensic settings.

Due to its pharmacological profile, fentanyl is classified as a controlled substance in most jurisdictions, and its use is strictly regulated. It is prescribed and administered only under medical supervision to minimize the risk of adverse effects, including respiratory depression, bradycardia, and sedation. Antagonists such as naloxone are used to reverse fentanyl-induced opioid toxicity in emergency situations.

In research and pharmaceutical development, fentanyl continues to serve as a model compound for the design of novel opioid analgesics. Its receptor binding properties and pharmacokinetic characteristics are extensively studied to develop safer and more effective pain management strategies. Despite its clinical value, fentanyl remains a substance of concern in public health due to the challenges associated with its misuse and the emergence of potent analogs in the illicit drug market.

References

2020. Instrumental and chemometric analysis of opiates via gas chromatography�vacuum ultraviolet spectrophotometry (GC-VUV). Analytical and Bioanalytical Chemistry, 412(3).
DOI: 10.1007/s00216-019-02337-5

2020. Evaluation of Trends of Near-Real-Time Urine Drug Test Results for Methamphetamine, Cocaine, Heroin, and Fentanyl. JAMA Network Open, 3(1).
DOI: 10.1001/jamanetworkopen.2019.18514

2020. Determination of Morphine, Fentanyl and Their Metabolites in Small Sample Volumes Using Liquid Chromatography Tandem Mass Spectrometry. Journal of Analytical Toxicology, 44(2).
DOI: 10.1093/jat/bkz104