Betahistine 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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C₈H₁₂N₂ · 2HCl         209.12

2-Pyridineethanamine, N-methyl-, dihydrochloride;

2-[2-(Methylamino)ethyl]pyridine, dihydrochloride CAS RN: 5579-84-0.

1 DEFINITION

Betahistine Hydrochloride contains NLT 99.0% and NMT 101.0% of betahistine hydrochloride (C₈H₁₂N₂ · 2HCl), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197A or 197K _{(CN 1-May-2020)}

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.

C. IDENTIFICATION TESTS-GENERAL (191), Chemical Identification Tests, Chloride: Meets the requirements

3 ASSAY

PROCEDURE

Solution A: 0.69 mg/mL of ammonium acetate in water. Adjust with glacial acetic acid to a pH of 4.7.

Mobile phase: Acetonitrile and Solution A containing 2.88 mg/mL of sodium lauryl sulfate (7:13)

Standard solution: 0.38 mg/mL of USP Betahistine Hydrochloride RS in Mobile phase

Sample solution: 0.38 mg/mL of Betahistine Hydrochloride in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 3.0-mm x 15-cm; 5-µm packing L1

Column temperature: 40°

Flow rate: 0.5 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of betahistine hydrochloride (C₈H₁₂N₂ · 2HCl) in the portion of Betahistine Hydrochloride taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of betahistine from the Sample solution

r_s = peak response of betahistine from the Standard solution

C_s = concentration of USP Betahistine Hydrochloride RS in the Standard solution (mg/mL)

C_u = concentration of Betahistine Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 99.0%–101.0% on the dried basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

ORGANIC IMPURITIES

Solution A, Mobile phase, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Analysis

Sample: Sample solution

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

Result = (r_U /r_T ) × 1/F × 100

r_U = peak response of each impurity from the Sample solution

r_T = sum of all the peak responses from the Sample solution

F = relative response factor of each impurity (see Table 1); 1.0 for all other peaks

Acceptance criteria: See Table 1.

Table 1

^a This impurity is a hydrochloride salt.

^b This impurity exists as a trihydrochloride.

5 SPECIFIC TESTS

PH (791).

Sample: 100 mg/mL of Betahistine Hydrochloride in water

Acceptance criteria: 2.0-3.0

LOSS ON DRYING (731)

Analysis: Dry between 100^o and 105^o to constant weight.

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

USP REFERENCE STANDARDS (11)

USP Betahistine Hydrochloride RS