Prilocaine

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 contains NLT 98.0% and NMT 102.0% of prilocaine (C₁₃H₂₀N₂O), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

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

Analysis: Because of the low melting point of prilocaine, the mortar, pestle, and potassium bromide must be at ambient temperature. Record the IR spectrum using the diffuse reflectance technique.

Acceptance criteria: Meets the requirements

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

Procedure

Buffer: 0.18 g/L of monobasic sodium phosphate and 2.89 g/L of dibasic sodium phosphate dihydrate in water

Mobile phase: Acetonitrile and Buffer (27:73)

System suitability solution: 2.5 µg/mL of USP Prilocaine RS and 3.0 µg/mL of USP Prilocaine Related Compound B RS in Mobile phase

Standard solution: 0.3 mg/mL of USP Prilocaine Hydrochloride RS in Mobile phase

Sample solution: 0.25 mg/mL of Prilocaine in Mobile phase

[Note—Sonication may be needed to aid dissolution for the Standard solution and the Sample solution.]

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm

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

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: At least 1.3 times the retention time of prilocaine

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 3.0 between prilocaine and prilocaine related compound B, System suitability solution

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 0.73, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of prilocaine (C₁₃H₂₀N₂O) in the portion of Prilocaine taken:

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × (M₁ / M₂) × 100

rᵤ = peak response of prilocaine from the Sample solution

rₛ = peak response of prilocaine from the Standard solution

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

Cᵤ = concentration of Prilocaine in the Sample solution (mg/mL)

M₁ = molecular weight of prilocaine, 220.31

M₂ = molecular weight of prilocaine hydrochloride, 256.77

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

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Limit of Prilocaine Related Compound A

Mobile phase and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 1.3 µg/mL of USP Prilocaine Related Compound A RS in Mobile phase

Sample solution: 10 mg/mL of Prilocaine in Mobile phase

System suitability

Sample: Standard solution

Suitability requirements

Signal-to-noise ratio: NLT 10

Analysis

Samples: Standard solution and Sample solution

Acceptance criteria: Any peak corresponding to prilocaine related compound A (o-toluidine) in the Sample solution is NMT the response of the major peak in the Standard solution (0.01%).

Organic Impurities

Buffer, Mobile phase, and System suitability solution: Proceed as directed in the Assay.

Sample solution: 2.5 mg/mL of Prilocaine in Mobile phase

Chromatographic system: Proceed as directed in the Assay, except for the run time.

Run time: At least 1.5 times the retention time of prilocaine

System suitability

Sample: System suitability solution

[Note—The relative retention times for prilocaine and prilocaine related compound B are about 1.0 and 1.2, respectively.]

Suitability requirements

Resolution: NLT 3.0 between prilocaine and prilocaine related compound B

Signal-to-noise ratio: NLT 10 for prilocaine

Analysis

Sample: Sample solution

Check the stability of the baseline by injecting Mobile phase.

Calculate the percentage of each impurity in the portion of Prilocaine taken:

Result = (rᵢ / rₜ) × 100

rᵢ = individual peak response for each impurity

rₜ = sum of all the peak responses

Acceptance criteria

Individual impurity: NMT 0.2% of any individual impurity; NMT one impurity exceeds 0.1%

Total impurities: NMT 0.5%

5 SPECIFIC TESTS

Water Determination, Method Ia 〈921〉

Sample: 1.00 g

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, and store below 25°.

USP Reference Standards 〈11〉

USP Prilocaine RS

USP Prilocaine Hydrochloride RS

USP Prilocaine Related Compound A RS

o-Toluidine hydrochloride.

C₇H₉N·HCl 143.62

USP Prilocaine Related Compound B RS

(RS)-N-(4-Methylphenyl)-2-(propylamino)propanamide.

C₁₃H₂₀N₂O 220.31