Homatropine Methylbromide

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

C₁₇H₂₄BrNO₃         370.28

8-Azoniabicyclo[3.2.1]octane, 3-(hydroxyphenylacetyl)oxy-8,8-dimethyl-, bromide, endo-(±)-;

3α-Hydroxy-8-methyl-1αH,5αH-tropanium bromide mandelate;

(1R,3s,5S)-3-[[(2RS)-2-Hydroxy-2-phenylacetyl]oxy]-8,8-dimethyl-8-azoniabicyclo[3.2.1]octane bromide CAS RN®: 80-49-9; UNII: 68JRS2HC1C.

1 DEFINITION

Homatropine Methylbromide contains NLT 98.0% and NMT 102.0% of C₁₇H₂₄BrNO₃, calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

[Note—If differences are observed, dissolve the specimen and the Reference Standard separately in methanol, and recrystallize by adding dioxane to each solution.]

B. Identification Tests—General, Bromide 〈191〉

Sample solution: 50 mg/mL in water

Acceptance criteria: Meets the requirements

3 ASSAY

Procedure

Solution A: 3.4 g/L of monobasic potassium phosphate and 5 g/L of 1-pentanesulfonic acid sodium salt in water. Adjust with a 330-g/L solution of phosphoric acid to a pH of 3.0.

Solution B: Acetonitrile and Solution A (3:2)

Diluent: Acetonitrile and Solution A (9:41)

Mobile phase: See the gradient table below.

System suitability solution: 0.01 mg/mL each of USP Homatropine Methylbromide RS and USP Homatropine Hydrobromide RS in Diluent Standard solution: 2.0 mg/mL of USP Homatropine Methylbromide RS in Diluent

Sample solution: 2.0 mg/mL of Homatropine Methylbromide in Diluent

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm × 15-cm; 3-µm packing L1

Flow rate: 1.4 mL/min

Injection size: 5 µL

3.2 System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for homatropine methylbromide and homatropine hydrobromide are 1.0 and 1.14, respectively.] Suitability requirements

Resolution: NLT 2.5 between homatropine methylbromide and homatropine hydrobromide, System suitability solution Tailing factor: NMT 1.5 for homatropine methylbromide peak, System suitability solution

Relative standard deviation: NMT 1%, Standard solution

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of C₁₇H₂₄BrNO₃  in the portion of Homatropine Methylbromide taken:

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

r_U = peak response of Homatropine Methylbromide from the Sample solution

r_S = peak response of homatropine methylbromide from the Standard solution

C_S = concentration of the Standard solution (mg/mL)

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

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

4 IMPURITIES

Inorganic Impurities

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Procedure

Solution A, Solution B, Diluent, Mobile phase, System suitability solution, and Sample solution: Proceed as directed in the Assay.

Standard solution: 0.01 mg/mL of USP Homatropine Methylbromide RS in Diluent

Chromatographic system: Proceed as directed in the Assay, except for injection size.

Injection size: 10 µL

4.1 System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 2.5 between homatropine methylbromide and homatropine hydrobromide

Tailing factor: NMT 1.5 for the homatropine methylbromide peak

4.2 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual impurity in the portion of Homatropine Methylbromide taken:

Result = (r_U /r_S )× (C_S /C_U) ×100

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

r_S= peak response of homatropine methylbromide from the Standard solution

C_S = concentration of the Standard solution (mg/mL)

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

[Note—Reporting level for impurities is 0.05%.]

4.3 Acceptance criteria

Individual impurities: See Impurity Table 1.

Total impurities: NMT 1.0%

[Note—Disregard the peak due to the bromide ion that elutes close to the solvent peak at about 1 min.]

Impurity Table 1

a(1R,3s,5S)-3-[[(2RS)-2-Hydroxy-2-phenylacetyl]oxy]-8,8-dimethyl-8-azoniabicyclo[3.2.1]oct-6-ene.

5 SPECIFIC TESTS

pH 〈791〉

Sample solution: 50 mg/mL in carbon dioxide-free water

Acceptance criteria: 4.5–6.5

Loss on Drying 〈731〉: Dry a sample at 105° to constant weight: it loses NMT 0.5% of its weight.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers. Store at room temperature.

USP Reference Standards 〈11〉

USP Homatropine Methylbromide RS

USP Homatropine Hydrobromide RS