Prilocaine Hydrochloride 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

Prilocaine Hydrochloride Injection is a sterile solution of Prilocaine Hydrochloride in Water for Injection. It contains NLT 95.0% and NMT 105.0% of the labeled amount of prilocaine hydrochloride (C₁₃H₂₀N₂O·HCl).

2 IDENTIFICATION

Delete the following:

▲A. Identification—Organic Nitrogenous Bases 〈181〉: Meets the requirements ▲2S (USP41)

Add the following:

▲A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.▲2S (USP41)

Delete the following:

▲B.

Sample: A volume of Injection equivalent to 300 mg of prilocaine hydrochloride

Analysis: Dilute the Sample with 5 mL of water, and add 4 mL of 6 N ammonium hydroxide. Extract with 50 mL of chloroform and filter the extract. Evaporate the filtrate on a steam bath with the aid of a current of air. Dissolve 100 mg of the prilocaine so obtained in 1 mL of alcohol, add 10 drops of cobaltous chloride TS, and shake for 2 min.

Acceptance criteria: A bright green color develops, and a precipitate is formed.▲2S (USP41)

Add the following:

▲B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.▲2S (USP41)

3 ASSAY

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Procedure

▲Solution A: Transfer 10 mL of glacial acetic acid to a 1000-mL volumetric flask containing 950 mL of water and dilute with water to volume. Adjust with ammonium hydroxide to a pH of 5.5.

Mobile phase: Acetonitrile and Solution A (21:79)

System suitability stock solution: 0.65 mg/mL of USP Prilocaine Related Compound A RS and 0.5 mg/mL of USP Prilocaine Related Compound B RS in Mobile phase

System suitability solution: 0.5 mg/mL of USP Prilocaine Hydrochloride RS, and 0.0065 mg/mL of USP Prilocaine Related Compound A RS and 0.005 mg/mL of USP Prilocaine Related Compound B RS from System suitability stock solution; in Mobile phase

Standard solution: 0.5 mg/mL of USP Prilocaine Hydrochloride RS in Mobile phase

Sample solution: Nominally 0.5 mg/mL of prilocaine hydrochloride from Injection in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm. For Identification B, use a diode array detector in the range of 210–400 nm.

Column: 4.6-mm × 15-cm; 5-µm packing L1

Column temperature: 35°

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: NLT 3 times the retention time of prilocaine

System suitability

Samples: System suitability solution and Standard solution

[Note—See Table 1 for relative retention times.]

Suitability requirements

Resolution: NLT 6.0 between prilocaine and prilocaine related compound B; NLT 4.0 between prilocaine related compound B and prilocaine related compound A, System suitability solution

Tailing factor: NMT 2.0, Standard solution

Relative standard deviation: NMT 1.0%, Standard solution▲2S (USP41)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of prilocaine hydrochloride (C₁₃H₂₀N₂O·HCl) in the volume of Injection taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak area from the Sample solution

rₛ = peak area from the Standard solution

Cₛ = concentration of USP Prilocaine Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of prilocaine hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 95.0%–105.0%

4 IMPURITIES

Add the following:

▲Organic Impurities

Solution A, Mobile phase, and System suitability solution: Prepare as directed in the Assay.

Standard solution: 0.01 mg/mL each of USP Prilocaine Hydrochloride RS and USP Prilocaine Related Compound A RS in Mobile phase

Sample solution: Nominally 5.0 mg/mL of prilocaine hydrochloride from Injection in Mobile phase

Chromatographic system: Proceed as directed in the Assay, except for Injection volume and Run time.

Injection volume: 30 µL

Run time: NLT 6.5 times the retention time of prilocaine

System suitability

Samples: System suitability solution and Standard solution

[Note—See Table 1 for relative retention times.]

Suitability requirements

Resolution: NLT 6.0 between prilocaine and prilocaine related compound B; NLT 4.0 between prilocaine related compound B and prilocaine related compound A, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of prilocaine related compound A in the portion of Injection taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak area of prilocaine related compound A from the Sample solution

rₛ = peak area of prilocaine related compound A from the Standard solution

Cₛ = concentration of USP Prilocaine Related Compound A RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of prilocaine hydrochloride in the Sample solution (mg/mL)

Calculate the percentage of any individual unspecified degradation product in the portion of Injection taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × 100

rᵤ = peak area of any individual unspecified degradation product from the Sample solution

rₛ = peak area of prilocaine from the Standard solution

Cₛ = concentration of USP Prilocaine Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of prilocaine hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: See Table 1.

Table 1

ᵃ Process impurity included in the table for identification only. Process impurities are controlled in the drug substance, and are not to be reported or included in the total impurities for the drug product.

▲2S (USP41)

5 SPECIFIC TESTS

Bacterial Endotoxins Test 〈85〉: NMT 0.9 USP Endotoxin Units/mg of prilocaine hydrochloride

pH 〈791〉: 6.0–7.0

Other Requirements: It meets the requirements in Injections and Implanted Drug Products 〈1〉.

6 ADDITIONAL REQUIREMENTS

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Packaging and Storage: Preserve in single-dose or multiple-dose containers, preferably of Type I glass. ▲Store at controlled room temperature. Protect from freezing.▲2S (USP41)

Change to read:

USP Reference Standards 〈11〉

▲▲ (CN 1-May-2018)

USP Prilocaine Hydrochloride RS

▲ USP Prilocaine Related Compound A RS

o-Toluidine hydrochloride.

C₇H₉N·HCl 143.61

USP Prilocaine Related Compound B RS

2-Propylamino-N-(p-tolyl)propanamide.

C₁₃H₂₀N₂O 220.31▲2S (USP41)