Sufentanil
[CAS# 56030-54-7]

Identification

• Classification: Analytical chemistry >> Standard >> Standard material
• Name: Sufentanil
• Synonyms: N-[4-(Methoxymethyl)-1-[2-(thiophen-2-yl)ethyl]piperidin-4-yl]-N-phenylpropionamide; R 30730; Sufentanyl
• Molecular Formula: C₂₂H₃₀N₂O₂S
• Molecular Weight: 386.55
• CAS Registry Number: 56030-54-7
• EC Number: 641-081-8
• SMILES: CCC(=O)N(C1=CC=CC=C1)C2(CCN(CC2)CCC3=CC=CS3)COC

Properties

• Solubility: Very slightly soluble (0.15 g/L) (25 ºC), Calc.^*
• Density: 1.1±0.1 g/cm³ Calc.^*, 1.20 g/cm^3**
• Melting point: 103-104 ºC^***
• Boiling point: 493.1±40.0 ºC 760 mmHg (Calc.)^*
• Flash point: 252.0±27.3 ºC (Calc.)^*
• Index of refraction: 1.577 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2014 ACD/Labs)

^** Peeters, O. M.; Acta Crystallographica, Section B: Structural Crystallography and Crystal Chemistry 1979, VB35(4), P999-1001.

^*** Srimurugan, Sankareswaran; Chemical & Pharmaceutical Bulletin 2009, V57(12), P1421-1424.

Safety Data

• Hazard Symbols: GHS06;GHS07 Danger
• Hazard Statements: H300-H310-H330-H336
• Precautionary Statements: P260-P261-P262-P264-P270-P271-P280-P284-P301+P316-P302+P352-P304+P340-P316-P319-P320-P321-P330-P361+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	2	H300
Acute toxicity	Acute Tox.	2	H310
Specific target organ toxicity - single exposure	STOT SE	3	H336
Acute toxicity	Acute Tox.	2	H330

• Controlled Substance: DEA Drug Code Number: 9740

Discovory and Applicatios

Sufentanil is a synthetic opioid analgesic derived from fentanyl and belongs to the class of μ-opioid receptor agonists. It is structurally similar to fentanyl but includes a thiophene ring in place of the phenyl ring and a methoxymethyl substituent, modifications that significantly enhance its potency. Sufentanil is considered one of the most potent opioids in clinical use, with analgesic strength estimated to be approximately five to ten times greater than that of fentanyl.

The compound was developed in the 1970s during efforts to create opioid analgesics with improved efficacy and pharmacokinetics for use in surgical anesthesia. It was designed to have a high affinity for the μ-opioid receptor, rapid onset, and relatively short duration of action, making it suitable for controlled anesthesia settings. Sufentanil gained clinical approval in several countries and is primarily administered intravenously or via epidural routes, particularly in the context of cardiac surgery, labor analgesia, and intensive care unit sedation.

One of the key features of sufentanil is its high lipid solubility, which allows it to rapidly cross the blood-brain barrier and bind effectively to central opioid receptors. This property contributes to its fast onset of action and allows precise control of sedation and analgesia when administered by trained personnel. Its use is generally limited to hospital settings under strict monitoring due to the significant risk of respiratory depression, especially when administered in high doses or in combination with other central nervous system depressants.

Sufentanil undergoes hepatic metabolism primarily via oxidative N-dealkylation and O-demethylation pathways catalyzed by cytochrome P450 enzymes. The resulting metabolites are mostly inactive and are excreted renally. The drug’s pharmacokinetic profile is influenced by factors such as age, liver function, and the presence of other medications that may inhibit or induce hepatic enzymes.

In clinical use, sufentanil is available in multiple formulations. One notable development is a sublingual tablet formulation approved for acute pain management in controlled settings. This formulation provides a non-invasive alternative for delivering potent analgesia with rapid absorption and ease of administration, particularly useful in military or emergency medical contexts. However, its distribution is tightly regulated to prevent misuse or diversion.

Due to its high potency, sufentanil carries a risk of serious adverse effects, including profound respiratory depression, bradycardia, muscle rigidity, and sedation. These effects necessitate careful titration and continuous monitoring of vital signs during administration. Naloxone, an opioid antagonist, is effective in reversing sufentanil-induced respiratory depression, although larger or repeated doses may be required due to the drug’s strong receptor binding.

In forensic and toxicological settings, sufentanil is occasionally encountered in cases of overdose or drug diversion. Although it is less commonly misused compared to fentanyl and its more accessible analogs, its presence in non-clinical environments raises concerns due to its extreme potency and low therapeutic index. Laboratory detection of sufentanil and its metabolites is typically conducted using liquid chromatography-tandem mass spectrometry methods, often as part of broader opioid screening panels.

While sufentanil remains an essential tool in modern anesthesia and pain management, its use is restricted to environments where advanced monitoring and resuscitative equipment are available. Its clinical applications reflect a balance between the need for powerful analgesia and the imperative to minimize risk through controlled administration and stringent oversight.

References

1990. Transdermal Delivery of Narcotic Analgesics: pH, Anatomical, and Subject Influences on Cutaneous Permeability of Fentanyl and Sufentanil. Pharmaceutical Research, 7(8).
DOI: 10.1023/a:1015912932416

1994. Intrathecal Sufentanil Compared to Epidural Bupivacaine for Labor Analgesia. Anesthesiology, 80(6).
DOI: 10.1097/00000542-199406000-00007

1998. Intrathecal Clonidine Combined with Sufentanil for Labor Analgesia. Anesthesiology, 88(3).
DOI: 10.1097/00000542-199803000-00015