Fentanyl Citrate Compounded Injection

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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1 DEFINITION

Fentanyl Citrate Compounded Injection contains NLT 90.0% and NMT 110.0% of the labeled amount of fentanyl (C₂₂H₂₈N₂O). It contains no bacteriostat or other preservative.

Prepare Fentanyl Citrate Compounded Injection, 50 mcg/mL, as follows (see Pharmaceutical Compounding—Sterile Preparations 〈797〉).

Dissolve Fentanyl Citrate in sufficient Sodium Chloride for Injection (0.9%) to bring to nal volume. Adjust with Sodium hydroxide solution or Hydrochloric acid solution to a pH of 4–7.5. Pass the solution through a suitable sterile filter of 0.22-µm pore size into appropriate sterile syringes or container(s). [Note—Do not use a cellulose ester filter membrane for sterilization due to potential for adsorption.]

2 ASSAY

Procedure

Solution A: Add 2.72 g of dibasic potassium phosphate to 800 mL of water. Adjust with phosphoric acid to a pH of 5.8. Add 200 mL of methanol and mix well.

Mobile phase: See Table 1.

Table 1

Standard solution: 2 mcg/mL of fentanyl prepared from USP Fentanyl Citrate RS in water

Sample solution: Transfer 1 mL of Injection into a 25-mL volumetric ask, and dilute with water to volume.

2.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm × 10-cm; 2.6-µm packing L1

Column temperature: 40°

Flow rate: 0.8 mL/min

Injection volume: 20 µL

2.2 System suitability

Sample: Standard solution

[Note—The retention time for fentanyl is about 24.6 min.]

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0% for replicate injections

2.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of fentanyl (C₂₂H₂₈N₂O) in the portion of Injection taken:

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

r_U = peak response of fentanyl from the Sample solution

r_S = peak response of fentanyl from the Standard solution

C_S = concentration of fentanyl in the Standard solution (mcg/mL)

C_U = nominal concentration of fentanyl in the Sample solution (mcg/mL)

Acceptance criteria: 90.0%–110.0%

3 SPECIFIC TESTS

pH 〈791〉: 4.0–7.5

Sterility Tests 〈71〉, Test for Sterility of the Product to Be Examined, Membrane Filtration: Meets the requirements

Bacterial Endotoxins Test 〈85〉: NMT 50.0 USP Endotoxin Units/mg of fentanyl

Particulate Matter in Injections 〈788〉: Meets the requirements

4 ADDITIONAL REQUIREMENTS

Packaging and Storage: Package in a light-resistant single-dose container. Store at controlled room temperature or in a refrigerator. Change to read:

Beyond-Use Date: In the absence of passing a sterility and endotoxin test, the beyond-use dates in Pharmaceutical Compounding—Sterile Preparations 〈797〉 apply. After successful completion of sterility and endotoxin testing, NMT 90 days after the date on which it was compounded when stored at controlled room temperature or in a refrigerator. _{(CN 1-May-2020)}

Labeling: Label it to indicate that it is for use in a single patient only, and to state the Beyond-Use Date.

USP Reference Standards 〈11〉

USP Fentanyl Citrate RS.