Methscopolamine Bromide

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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C₁₈H₂₄BrNO₄ 398.29

3-Oxa-9-azoniatricyclo[3.3.1.02,4]nonane, 7-(3-hydroxy-1-oxo-2-phenylpropoxy)-9,9-dimethyl-, bromide, [7(S)-(1α,2β,4β,5α,7β]-;

6β,7β-Epoxy-3α-hydroxy-8-methyl-1αH,5αH-tropanium bromide (−)-tropate;

(1R,2R,4S,5S,7s)-7-{[(S)-3-Hydroxy-2-phenylpropanoyl]oxy}-9,9-dimethyl-3-oxa-9-azatricyclo[3.3.1.02,4]nonan-9-ium bromide CAS RN®: 155-41- 9; UNII: RTN51LK7WL.

1 DEFINITION

Methscopolamine Bromide contains NLT 97.0% and NMT 103.0% of methscopolamine bromide (C₁₈H₂₄BrNO₄ ), 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. Identification Tests—General 〈191〉, Chemical Identification Tests, Bromide

Sample solution: 50 mg/mL in water

Acceptance criteria: Meets the requirements

3 ASSAY

Procedure

Buffer: A solution containing 5.16 g/L of sodium 1-hexanesulfonate monohydrate and 3.40 g/L of monobasic potassium phosphate in water, adjusted with 1 M phosphoric acid to a pH of 2.8

Solution A: Acetonitrile and Buffer (15:85)

Solution B: Acetonitrile and Buffer (50:50)

Mobile phase: See Table 1. Return to original conditions and re-equilibrate the system.

Table 1

Standard solution: 1.0 mg/mL of USP Methscopolamine Bromide RS in Solution A

Sample solution: 1.0 mg/mL of Methscopolamine Bromide in Solution A

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 4.6-mm × 10.0-cm; monolithic packing L1

Column temperature: 50°

Flow rate: 3 mL/min

Injection volume: 5 μL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 1% for 6 replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of methscopolamine bromide (C₁₈H₂₄BrNO₄) in the portion of Methscopolamine Bromide taken:

Result = (r_U/r_S)x(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 Methscopolamine Bromide RS in the Standard solution (mg/mL)

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

Acceptance criteria: 97.0%–103.0% on the dried basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Buffer, Solution A, Solution B, Mobile phase, and Sample solution: Prepare as directed in the Assay.

Scopolamine hydrobromide solution: 0.05 mg/mL of USP Scopolamine Hydrobromide RS in Solution A

System suitability solution: 1.0 mg/mL of USP Methscopolamine Bromide RS and 1.0 μg/mL of USP Scopolamine Hydrobromide RS in

Solution A, from the Scopolamine hydrobromide solution. [Note—This solution contains 0.1% of scopolamine hydrobromide.]

Standard stock solution: Prepare as directed for the Standard solution in the Assay.

Diluted standard solution: 0.5 μg/mL of USP Methscopolamine Bromide RS in Solution A, from the Standard stock solution

Chromatographic system: Proceed as directed in the Assay.

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 1.5 between methscopolamine and scopolamine

Tailing factor: NMT 2.0 for the methscopolamine peak

Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the portion of Methscopolamine Bromide taken:

Result = (r_U /r_S ) × (1/F) × 100

r_U = peak area of any impurity from the Sample solution

r_S = peak area of methscopolamine from the Sample solution

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. Disregard any peak with an area less than that of the methscopolamine peak of the Diluted standard

solution, and disregard any peak that is due to Solution A.

Table 2

^a (1R,3r,5S)-3-[(3-Hydroxy-2-phenylpropanoyl)oxy]-8,8-dimethyl-8-azabicyclo[3.2.1]octan-8-ium bromide.

^b (1R,2R,4S,5S,7s)-9,9-Dimethyl-7-[(2-phenylacryloyl)oxy]-3-oxa-9-azatricyclo[3.3.1.02,4]nonan-9-ium bromide.

5 SPECIFIC TESTS

Optical Rotation 〈781S〉, Procedures, Specific Rotation

Sample solution: 50 mg/mL in water

Acceptance criteria: −21° to −25°

Loss on Drying 〈731〉

Analysis: Dry at 105° for 2 h.

Acceptance criteria: NMT 2.0%

6 ADDITIONAL REQUIREMENTS

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

USP Reference Standards 〈11〉

USP Methscopolamine Bromide RS

USP Scopolamine Hydrobromide RS