Mepivacaine Hydrochloride and Levonordefrin 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

Mepivacaine Hydrochloride and Levonordefrin Injection is a sterile solution of Mepivacaine Hydrochloride and Levonordefrin in Water for Injection. It contains NLT 95.0% and NMT 105.0% of the labeled amount of mepivacaine hydrochloride (C₁₅H₂₂N₂O · HCl) and NLT 90.0% and NMT 110.0% of the labeled amount of levonordefrin (C₉H₁₃NO₃).

2 IDENTIFICATION

A.

Analysis: Extract a volume of Injection, equivalent to 200 mg of mepivacaine, with two 10-mL portions of ether, and discard the ether extracts.

Render slightly alkaline with sodium carbonate TS, extract the precipitate with ether, evaporate the ether extract on a steam bath to dryness, and dry the residue under vacuum at 60° for 1h.

Acceptance criteria: The mepivacaine obtained melts between 149° and 153°.

B. Identification Tests—General, Chloride 〈191〉: Meets the requirements

3 ASSAY

Mepivacaine Hydrochloride

Buffer: 3.40 g/L of monobasic potassium phosphate and 4.35 g/L of dibasic potassium phosphate in water. Adjust with potassium hydroxide or phosphoric acid to a pH of 6.3.

Mobile phase: Acetonitrile and Buffer (35:65)

System suitability solution: 0.05 mg/mL of methylparaben and 1.0 mg/mL of USP Mepivacaine Hydrochloride RS in Mobile phase

Standard solution: 1.0 mg/mL of USP Mepivacaine Hydrochloride RS in Mobile phase

Sample solution: Nominally 1 mg/mL of mepivacaine hydrochloride from Injection in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 263 nm

Column: 4.6-mm × 25-cm; 5-μm packing L11

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 10 μL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for mepivacaine and methylparaben are 1.0 and 1.4, respectively.]

Suitability requirements

Resolution: NLT 2.0 between methylparaben and mepivacaine, System suitability solution

Capacity factor: NLT 1.0 for the mepivacaine peak, System suitability solution

Tailing factor: NMT 2.0 for the mepivacaine peak, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of mepivacaine hydrochloride (C₁₅H₂₂N₂O · HCl) in the volume of Injection 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 Mepivacaine Hydrochloride RS in the Standard solution (mg/mL)

C_U = nominal concentration of mepivacaine hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 95.0%–105.0%

Levonordefrin

Ferro-citrate solution and Buffer solution: Prepare as directed in Epinephrine Assay 〈391〉.

Standard stock solution: With the aid of 20 mL of sodium bisulfite solution (1 in 50), transfer 25 mg of USP Levonordefrin RS to a 50-mL volumetric flask, and dilute with water to volume.

Standard solution: 50 μg/mL of USP Levonordefrin RS in sodium bisulfite solution (1 in 500) from the Standard stock solution. Make the final dilution at the time the Assay is to be carried out.

Sample solution: Nominally 50 μg/mL of levonordefrin from Injection, diluting if necessary

Analysis: Proceed as directed in Epinephrine Assay 〈391〉, except use levonordefrin wherever epinephrine [base] is called for. When the Ferro-citrate solution and the Buffer solution are mixed with the Sample solution, a fine precipitate may be formed. Remove this precipitate by centrifugation or by passing through dry filter paper before the colorimetric measurements are taken.

Calculate the percentage of the labeled amount of levonordefrin (C₉H₁₃NO₃) in the volume of Injection taken:

Result = (A_U/A_S) × (C_S/C_U) × 100

A_U = absorbance of the Sample solution

A_S = absorbance of the Standard solution

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

C_U = nominal concentration of levonordefrin in the Sample solution (μg/mL)

Acceptance criteria: 90.0%–110.0%

4 SPECIFIC TESTS

Color and Clarity

Standard solution: Transfer 2.0 mL of 0.100 N iodine VS to a 500-mL volumetric flask, and dilute with water to volume.

Analysis

Samples: Standard solution and Sample solution

Visually examine a portion of the Injection (Sample solution) in a suitable clear glass test tube against a white background: it is not pinkish, and it contains no precipitate. If any yellow color is observed in the Sample solution, concomitantly determine the absorbances of the Sample solution and Standard solution in 1-cm cells with a suitable spectrophotometer set at 460 nm.

Acceptance criteria: The absorbance of the Sample solution does not exceed that of the Standard solution.

pH 〈791〉 : 3.3–5.5

Bacterial Endotoxins Test 〈85〉 : It contains NMT 0.8 USP Endotoxin Unit/mg of mepivacaine hydrochloride.

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

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose or multiple-dose containers, preferably of Type I glass.

Labeling: The label indicates that the Injection is not to be used if its color is pinkish or darker than slightly yellow or if it contains a precipitate.

USP Reference Standards 〈11〉

USP Levonordefrin RS

USP Mepivacaine Hydrochloride RS