Mepivacaine 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

Mepivacaine Hydrochloride contains NLT 98.0% and NMT 102.0% of mepivacaine hydrochloride (C₁₅H₂₂N₂O · HCl), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

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

Sample solution: 10 mg/mL

Acceptance criteria: Meets the requirements

3 ASSAY

Procedure

Buffer: 2.25 g/L solution of phosphoric acid, adjusted with 50% sodium hydroxide to a pH of 7.6

Mobile phase: Acetonitrile and Buffer (35:65)

System suitability solution: 2 μg/mL of USP Mepivacaine Hydrochloride RS and 3 μg/mL of USP Bupivacaine Related Compound B RS in Mobile phase

Standard solution: 0.2 mg/mL of USP Mepivacaine Hydrochloride RS in Mobile phase

Sample solution: 0.2 mg/mL of Mepivacaine Hydrochloride in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

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

Flow rate: 1 mL/min

Injection volume: 20 μL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2.5 between bupivacaine related compound B and mepivacaine, System suitability solution

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

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

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

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

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Mobile phase, System suitability solution, and Chromatographic system: Proceed as directed in the Assay. The run time is three times the retention time of the mepivacaine peak.

Standard solution: 2 μg/mL of USP Mepivacaine Hydrochloride RS in Mobile phase

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

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 2.5 between bupivacaine related compound B and mepivacaine, System suitability solution

Tailing factor: NMT 1.5, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any impurity in the portion of Mepivacaine Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of any individual impurity from the Sample solution

r_S = peak response of mepivacaine from the Standard solution

C_S = concentration of USP Mepivacaine Hydrochloride RS in the Standard solution (mg/mL)

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

Acceptance criteria: See Table 1.

Table 1

^a N-(2,6-Dimethylphenyl)piperidine-2-carboxamide.

^b N-(2,6-Dimethylphenyl)picolinamide.

2,6-Dimethylaniline

Prepare the Standard solution and Sample solution fresh, just before use.

Standard stock solution: 0.6 μg/mL of USP Ropivacaine Related Compound A RS in 1 N hydrochloric acid. [Note—Ropivacaine related compound A is 2,6-dimethylaniline hydrochloride.]

Standard solution: Transfer 2.0 mL of the Standard stock solution and 1.0 mL of 3 N sodium hydroxide to a 20-mL headspace vial, and immediately close the vial with a cap.

Sample stock solution: 30 mg/mL of Mepivacaine Hydrochloride in 1 N hydrochloric acid

Sample solution: Transfer 2.0 mL of the Sample stock solution and 1.0 mL of 3 N sodium hydroxide to a 20-mL headspace vial, and immediately close the vial with a cap.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 0.53-mm × 30-m capillary; coated with 3-μm

lm of G43

Temperatures

Injection port: 225°

Detector: 250°

Column: See Table 2.

Table 2

Carrier gas: Helium

Flow rate: 4 mL/min

Injection type: Split ratio, 1:1

Headspace sampler

Equilibration time: 15 min

Equilibration temperature: 90°

Loop temperature: 215°

Transfer line temperature: 220°

Vial pressure: About 15 psi

Loop size: 3 mL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 15%

Analysis

Samples: Standard solution and Sample solution

Calculate the quantity, in ppm, of 2,6-dimethylaniline in the portion of Mepivacaine Hydrochloride taken:

Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 106

r_U = peak response of 2,6-dimethylaniline from the Sample solution

r_S = peak response of 2,6-dimethylaniline from the Standard solution

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

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

M_r1 = molecular weight of 2,6-dimethylaniline, 121.18

M_r2 = molecular weight of 2,6-dimethylaniline hydrochloride (ropivacaine related compound A), 157.64

Acceptance criteria: NMT 20 ppm

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry at 105° for 4 h.

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers.

Change to read:

USP Reference Standards 〈11〉

USP Bupivacaine Related Compound B RS

N-(2,6-Dimethylphenyl)piperidine-2-carboxamide hydrochloride.

C₁₄H₂₀N₂O · HCl 268.79▲ (ERR 1-Oct-2018)

USP Mepivacaine Hydrochloride RS

USP Ropivacaine Related Compound A RS

2,6-Dimethylaniline hydrochloride.