Sufentanil Citrate

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

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

DOWNLOAD PDF HERE

C₂₂H₃₀N₂O₂S · C₆H₈O₇ 578.67

Propanamide, N-[4-(methoxymethyl)-1-[2-(thienyl)ethyl]-4-piperidinyl]-N-phenyl-, 2-hydroxy-1,2,3-propanetricarboxylate (1:1);

N-[4-(Methoxymethyl)-1-[2-(2-thienyl)ethyl]-4-piperidyl]propionanilide citrate (1:1) CAS RN®: 60561-17-3; UNII: S9ZFX8403R.

1 DEFINITION

Sufentanil Citrate contains NLT 98.0% and NMT 102.0% of sufentanil citrate (C₂₂H₃₀N₂O₂S · C₆H₈O₇), calculated on the dried basis.

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

2 IDENTIFICATION

Change to read:

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

Change to read:

B. Spectroscopic Identification Tests 〈197〉, Ultraviolet-Visible Spectroscopy: 197U (CN 1-May-2020)

Sample solution: 50 μg/mL

Medium: Use Mobile phase, prepared as directed in the Assay.

Acceptance criteria: Meets the requirements

C. Identification Tests—General, Citrate 〈191〉

Sample solution: Dissolve 500 mg in 5 mL of water.

Analysis: Render the Sample solution alkaline with 1 N sodium hydroxide, and extract with three 5-mL portions of methylene chloride.

Acceptance criteria: The aqueous layer meets the requirements.

D. 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: Methanol, acetonitrile, and 0.13 M ammonium acetate (45:24:31). Adjust with glacial acetic acid or ammonium hydroxide to a pH of 7.2.

Standard solution: 0.075 mg/mL of USP Sufentanil Citrate RS in Mobile phase

Sample solution: 0.075 mg/mL of Sufentanil Citrate in Mobile phase

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 228 nm

Column: 4.6-mm × 25-cm; packing L1

Flow rate: 1.5 mL/min

Injection volume: 100 μL

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.73%

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of sufentanil citrate (C₂₂H₃₀N₂O₂S · C₆H₈O₇) in the portion of Sufentanil Citrate taken:

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 Sufentanil Citrate RS in the Standard solution (mg/mL)

C_U = concentration of Sufentanil Citrate in the Sample solution (mg/mL)

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

4 IMPURITIES

4.1 Organic Impurities

Mobile phase: Proceed as directed in the Assay.

Blank: 0.664 mg/mL of citric acid in Mobile phase

Sample solution: 0.75 mg/mL of Sufentanil Citrate in Mobile phase

Chromatographic system: Proceed as directed in the Assay.

4.2 Analysis

Samples: Blank and Sample solution

Calculate the percentage of each impurity, disregarding any peaks corresponding to those found in the Blank, in the portion of Sufentanil

Citrate taken:

Result = (r_U/r_T) × 100

r_U = peak response for each impurity

r_T = sum of the responses of all of the peaks

Acceptance criteria

Individual impurity: NMT 0.5%

Total impurities: NMT 1.0%

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry a sample under vacuum at 60° for 2 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Store at 25°, excursions permitted between 15° and 30°.

USP Reference Standards 〈11〉

USP Sufentanil Citrate RS