Mexiletine 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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C₁₁H₁₇NO · HCl          215.72

2-Propanamine, 1-(2,6-dimethylphenoxy)-, hydrochloride, (±)-;

(+)-1-Methyl-2-(2,6-xylyloxy) ethylamine hydrochloride    CAS RN^®: ^▲5370-01-4. _{▲(ERR 1-May-2020)}

1 DEFINITION

Mexiletine Hydrochloride contains NLT 98.0% and NMT 102.0% of mexiletine hydrochloride (C₁₁H₁₇NO · HCl), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. ^▲SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197M_{▲(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.

Sample solution: 3 mL of a solution (1 in 60)

Analysis: Add 1 mL of 6 N ammonium hydroxide to the Sample solution, filter, and acidify the filtrate with 2 mL of nitric acid. Then add 1 mL of silver nitrate TS.

Acceptance criteria: A curdy, white precipitate is formed, and it is soluble in an excess of 6 N ammonium hydroxide (presence of chloride).

3 ASSAY

PROCEDURE

Buffer: Dissolve 11.5 g of anhydrous sodium acetate in 500 mL of water. Add 3.2 mL of glacial acetic acid, mix, and allow to cool. Adjust with hydrochloric acid to a pH of 4.8 ± 0.1, and dilute with water to 1000 mL.

Mobile phase: Methanol and Buffer (600:400)

Standard solution: 2 mg/mL of USP Mexiletine Hydrochloride RS in Mobile phase

System suitability solution: 1 mg/mL of 2-phenylethylamine hydrochloride in Standard solution

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

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Columns

Guard: Packing L1

Analytical: 3.9-mm x 30-cm; 10-µm packing L1

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Samples: Standard solution and System suitability solution

[NOTE-The relative retention times for 2-phenylethylamine and mexiletine are 0.7 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 3.0 between the 2-phenylethylamine and mexiletine peaks, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of mexiletine hydrochloride (C₁₁H₁₇NO · HCl) in the portion of Mexiletine Hydrochloride taken: 

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak area of mexiletine from the Sample solution

r_S = peak area of mexiletine from the Standard solution 

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

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

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

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 ORGANIC IMPURITIES

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

Standard solution: 0.2 mg/mL of USP Mexiletine Hydrochloride RS in Mobile phase, from the Standard solution in the Assay

Sample solution: 20 mg/mL of Mexiletine Hydrochloride in Mobile phase

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for 2-phenylethylamine and mexiletine are 0.7 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 3.0 between the 2-phenylethylamine and mexiletine peaks, System suitability solution

Relative standard deviation: NMT 3.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Mexiletine Hydrochloride taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak area of each impurity from the Sample solution

r_S = peak area of mexiletine from the Standard solution

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

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

Acceptance criteria

Any individual impurity: NMT 1%

Total impurities: NMT 1.5%

5 SPECIFIC TESTS

5.1 PH (791).

Sample solution: 100 mg/mL

Acceptance criteria: 3.5-5.5

5.2 LOSS ON DRYING (731)

Analysis: Dry at 105° for 2 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

USP REFERENCE STANDARDS (11)

USP Mexiletine Hydrochloride RS