Fentanyl Citrate and Bupivacaine Hydrochloride 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 and Bupivacaine Hydrochloride Compounded Injection contains NLT 90.0% and NMT 110.0% of the labeled amount of fentanyl (C₂₂H₂₈N₂O) and bupivacaine hydrochloride (C₁₈H₂₈N₂O · HCl). It contains no bacteriostat or other preservative.

Prepare Fentanyl Citrate and Bupivacaine Hydrochloride Compounded Injection containing 2000 mcg/mL of fentanyl and 10 mg/mL of bupivacaine hydrochloride as follows (see Pharmaceutical Compounding—Sterile Preparations 〈797〉).

Dissolve Fentanyl Citrate, Bupivacaine Hydrochloride, and Sodium Chloride in Sterile Water for Injection. Pass the solution through a sterile lter of 0.22-µm pore size into appropriate sterile container(s).

[Note—Do not use a cellulose ester lter membrane for sterilization due to potential for adsorption.]

2 ASSAY

2.1 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 and 0.075 mg/mL of bupivacaine hydrochloride prepared from USP Fentanyl Citrate RS and USP Bupivacaine Hydrochloride RS in water

Bupivacaine hydrochloride sample solution: Transfer 0.75 mL of Injection into a 100-mL volumetric ask, and dilute with water to volume. Fentanyl sample solution: Transfer 0.1 mL of Injection into a 100-mL volumetric ask, and dilute with water to volume.

2.2 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

2.3 System suitability

Sample: Standard solution

[Note—The retention times for bupivacaine hydrochloride and fentanyl are about 21.5 and 24.6 min, respectively.]

Suitability requirements

Tailing factor: NMT 2.0 for both fentanyl and bupivacaine hydrochloride

Relative standard deviation: NMT 2.0% for both fentanyl and bupivacaine hydrochloride from replicate injections

2.4 Analysis

Samples: Standard solution and sample solution

Calculate the percentage of the labeled amount of fentanyl (C₂₂H₂₈N₂O) and bupivacaine hydrochloride (C₁₈H₂₈N₂O · HCl) in the portion of Injection taken:

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

r_U = peak response of fentanyl or bupivacaine hydrochloride from the sample solution

r_S = peak response of fentanyl or bupivacaine hydrochloride from the Standard solution

C_S = concentration of fentanyl or bupivacaine hydrochloride in the Standard solution (mcg/mL or mg/mL, respectively) 

C_U = nominal concentration of fentanyl or bupivacaine hydrochloride in the sample solution (mcg/mL or mg/mL, respectively) 

Acceptance criteria: 90.0%–110.0%

3 SPECIFIC TESTS

pH 〈791〉: 3.1–4.1

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

Bacterial Endotoxins Test 〈85〉: It contains NMT 50.0 USP Endotoxin Units/mg of fentanyl and NMT 2.5 USP Endotoxin Units/mg of bupivacaine hydrochloride.

Particulate Matter in Injections 〈788〉: Meets the requirements

3.1 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: The label bears a warning that this is a very high-strength injection. [Note—This is a high-strength injection.]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 Bupivacaine Hydrochloride RS

USP Fentanyl Citrate RS.