Alfentanil Hydrochloride

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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C₂₁H₃₂N₆O₃ · HCl · H₂O 470.99

C₂₁H₃₂N₆O₃· HCI 452.98

Propanamide, N-[1-[2-(4-ethyl-4,5-dihydro-5-oxo-1H-tetrazol-1-yl)ethyl]-4-(methoxymethyl)-4-piperidinyl]-N-phenyl, monohydrochloride, monohydrate;

N-[1-[2-(4-Ethyl-5-oxo-2-tetrazolin-1-yl)-ethyl]-4-(methoxymethyl)-4-piperidyl]propionanilide monohydrochloride monohydrate CAS RN®: 70879- 28-6; UNII: 11S92G0TIW.

Anhydrous CAS RN®: 69049-06-5; UNII: 333JTI7A2M.

1 DEFINITION

Alfentanil Hydrochloride contains NLT 98.0% and NMT 102.0% of alfentanil hydrochloride (C₂₁H₃₂N₆O₃ · HCl ), calculated on the anhydrous basis

[Caution—Handle Alfentanil Hydrochloride with great care because it is a potent opioid analgesic. Great care should be taken to prevent inhaling particles of Alfentanil Hydrochloride and exposing the skin to it.]

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 Procedure

Mobile phase: Acetonitrile and 0.01 M tetrabutylammonium hydrogen sulfate (14:86)

Standard solution: 0.54 mg/mL of USP Alfentanil Hydrochloride RS in Mobile phase

Sample solution: 0.54 mg/mL of Alfentanil Hydrochloride in Mobile phase

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 235 nm

Column: 4.0-mm × 25-cm; 5-µm packing L1

Flow rate: 2 mL/min

Injection volume: 25 µL

System suitability

Sample: Standard solution

Suitability requirements

Column eciency: NLT 5400 theoretical plates

Tailing factor: NMT 1.3

Relative standard deviation: NMT 0.73%

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of alfentanil hydrochloride (C H N O  · HCl) in the portion of Alfentanil Hydrochloride taken: 21 32 6 3

Result = (r_U /r_S ) × (C_S /C_U ) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of USP Alfentanil Hydrochloride RS in the Standard solution (mg/mL) 

C_U = concentration of Alfentanil Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the anhydrous basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

4.1 Organic Impurities

Mobile phase: Acetonitrile and 0.01 M tetrabutylammonium hydrogen sulfate (14:86) Standard solution: 0.54 mg/mL of USP Alfentanil Hydrochloride RS in Mobile phase Sample solution: 0.54 mg/mL of Alfentanil Hydrochloride in Mobile phase

4.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 235 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Flow rate: 2 mL/min

Injection volume: 25 µL

System suitability

Sample: Standard solution

Suitability requirements

Column eciency: NLT 5400 theoretical plates

Tailing factor: NMT 1.3

Relative standard deviation: NMT 0.73%

4.3 Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the portion of Alfentanil Hydrochloride taken:

Result = (r_U /r_T ) × 100

r_U = peak response for each impurity

r_T = sum of all the peak responses

Acceptance criteria

Any single impurity: NMT 0.5%

Total impurities: NMT 1.0%

5 SPECIFIC TESTS

Water Determination, Method I 〈921〉: NMT 4.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP Alfentanil Hydrochloride RS