Lidocaine Hydrochloride

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

Lidocaine Hydrochloride contains NLT 97.5% and NMT 102.5% of lidocaine hydrochloride (C₁₄H₂₂N₂O · HCl), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS 〈197〉 , Infrared Spectroscopy (CN 1-M -2020)

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

C. IDENTIFICATION TESTS—GENERAL, Chloride〈191〉: Meets the requirements

3 ASSAY

3.1 PROCEDURE

Solution A: Water and glacial acetic acid (930:50). Adjust with 1 N sodium hydroxide to a pH of 3.40. Mobile phase: Acetonitrile and Solution A (1:4)

Standard solution: 2.0 mg/mL of USP Lidocaine Hy drochloride RS in Mobile phase System suitability stock solution: 220 µg/mL of methylparaben in Mobile phase

System suitability solution: Mix 2 mL of System suitability stock solution and 20 mL of Standard solution.

Sample solution: 2 mg/mL of Lidocaine Hydrochloride in Mobile phase

3.1.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.) Mode: LC

Detector: UV 254 nm

Column: 3.9-mm × 30-cm; packing L1 Flow rate: 1.5 mL/min

Injection volume: 20 µL

3.1.2 System suitability

Samples: Standard solution and System suitability solution

Suitability requirements

Resolution: NLT 3.0 between lidocaine and methylparaben, System suitability solution Relative standard deviation: NMT 1.5%, Standard solution

3.1.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of lidocaine hydrochloride (C₁₄H₂₂N₂O · HCl) in the portion of Lidocaine Hydrochloride 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 Lidocaine Hy drochloride RS in the Standard solution (mg/mL)

C_U = concentration of Lidocaine Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 97.5%–102.5% on the anhydrous basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION 〈281〉

NMT 0.1%

4.2 CHLORIDE AND SULFATE, Sulfate〈221〉

Sample: 100 mg

Analysis: Dissolve Sample in 10 mL of water, and add 1 mL of 3 N hydrochloric acid. Mix, and add 1 mL of barium chloride TS. Acceptance criteria: The turbidity does not exceed that produced by 0.10 mL of 0.020 N sulfuric acid (NMT 0.1%).

4.3 ORGANIC IMPURITIES

Buffer: 4.85 g/L of monobasic potassium phosphate in water. Adjust with sodium hydroxide solution to a pH of 8.0. Mobile phase: Acetonitrile and Buffer (30:70)

Standard solution: 0.5 µg/mL of USP Ropivacaine Related Compound A RS and 5 µg/mL each of USP Lidocaine Related Compound H RS and USP Lidocaine Hy drochloride RS in Mobile phase

Sample solution: 5 mg/mL of Lidocaine Hydrochloride in Mobile phase

4.3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 3.9-mm × 15-cm; 5-µm packing L1

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 20 µL

Run time: NLT 3.5 times the retention time for lidocaine

4.3.2 System suitability

Sample: Standard solution

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

Suitability requirements

Resolution: NLT 1.5 between lidocaine related compound H and ropivacaine related compound A; NLT 2.0 between ropivacaine related compound A and lidocaine

Relative standard deviation: NMT 10.0% for ropivacaine related compound A

4.3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of lidocaine related compound H or ropivacaine related compound A in the portion of Lidocaine Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response for lidocaine related compound H or ropivacaine related compound A from the Sample solution

r_S = peak response of lidocaine related compound H or ropivacaine related compound A from the Standard solution

C_S = concentration of USP Lidocaine Related Compound H RS or USP Ropivacaine Related Compound A RS in the Standard solution (µg/mL)

C_U = concentration of Lidocaine Hydrochloride in the Sample solution (µg/mL)

Calculate the percentage of any individual unspecified impurity in the portion of Lidocaine Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response for each unspecified impurity from the Sample solution

r_S = peak response of lidocaine from the Standard solution

C_S = concentration of USP Lidocaine Hydrochloride RS in the Standard solution (µg/mL)

C_U = concentration of Lidocaine Hydrochloride in the Sample solution (µg/mL)

Acceptance criteria: See Table 1.

Table 1

5 SPECIFIC TESTS

WATER DETERMINATION, Method I〈921〉: 5.0%–7.0%

STERILITY TESTS 〈71〉: Where the label states that Lidocaine Hydrochloride is sterile, it meets the requirements.

BACTERIAL ENDOTOXINS TEST 〈85〉: Where the label states that Lidocaine Hydrochloride is sterile or must be subjected to further processing during the preparation of injectable dosage forms, it contains NMT 1.1 USP Endotoxin Units/mg of lidocaine hydrochloride.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed containers. Store at controlled room temperature.

LABELING: Where it is intended for use in preparing injectable dosage forms, the label states that it is sterile or must be subjected to further processing during the preparation of injectable dosage forms.

USP REFERENCE STANDARDS 〈11〉

USP Lidocaine Hydrochloride RS

USP Lidocaine Related Compound H RS

2-Chloro-N-(2,6-dimethylphenyl)acetamide. C₁₀H₁₂ClNO    197.66

USP Ropivacaine Related Compound A RS

2,6-Dimethylaniline hydrochloride. C₈H₁₁N · HCl    157.64