Methscopolamine Bromide Tablets

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

Methscopolamine Bromide Tablets contain NLT 93.0% and NMT 107.0% of the labeled amount of methscopolamine bromide (C₁₈H₂₄BrNO₄).

2 IDENTIFICATION

A. Thin-Layer Chromatographic Identification Test 〈201〉 pH 7.3 dye–buffer solution: Prepare a solution containing, in each 500 mL, 200 mg of bromothymol blue, 3.2 mL of 0.1 N sodium hydroxide, 577.5 mg of citric acid monohydrate, and 6.3 mg of anhydrous dibasic sodium phosphate.

Standard solution: Prepare 0.025 mg/mL of USP Methscopolamine Bromide RS in water. Transfer 10 mL of this solution to a vessel containing 10 mL of chloroform and 10 mL of pH 7.3 dye–buffer solution. Shake vigorously for 3 min, centrifuge, and transfer 8 mL of the chloroform layer to a suitable container. Evaporate to dryness, and dissolve the residue in 1 mL of chloroform.

Sample solution: Finely powder 1 Tablet, and transfer an amount equivalent to 0.5 mg of methscopolamine bromide to a suitable container.

Add 20 mL of water, heat for 5 min on a steam bath with frequent agitation, and centrifuge to obtain a clear supernatant. Transfer 10 mL of the supernatant to a vessel containing 10 mL of chloroform and 10 mL of pH 7.3 dye–buffer solution. Shake vigorously for 3 min, centrifuge, and transfer 8 mL of the chloroform layer to a suitable container. Evaporate to dryness, and dissolve the residue in 1 mL of chloroform.

Application volume: 50 μL

Developing solvent system: Butyl alcohol, water, and glacial acetic acid (4:5:1). Transfer a measured volume of the upper organic layer to a suitable container, and mix with a volume of alcohol equivalent to 20% of the volume of the organic layer.

Spray reagent: Potassium–bismuth iodide TS

Analysis

Samples: Standard solution and Sample solution

Allow the solvent front to move three-fourths of the length of the plate, remove the plate from the developing chamber, mark the solvent front, and dry the plate under a current of air for 30 min. Spray the plate evenly with Spray reagent.

Acceptance criteria: The chromatogram of the Sample solution shows a bright orange spot on a yellow background corresponding in R value

(0.25) to that of the Standard solution. [Note—Bromothymol blue produces a dark yellow spot at an R value of 0.8.]

Change to read:

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.2S

(USP41)

3 ASSAY

Change to read:

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: Buffer

Solution B: Acetonitrile

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

Table 1

Diluent: Acetonitrile and Buffer (13:87)

Standard solution: 0.125 mg/mL of USP Methscopolamine Bromide RS in Diluent

Sample solution: Place 10 Tablets in a 200-mL volumetric flask. Add about 180 mL of Diluent, and sonicate for 30 min. Shake by mechanical means for 30 min, dilute with Diluent to volume, and mix. Further dilute with Diluent, if needed, to obtain the solution with a nominal concentration of 0.125 mg/mL of methscopolamine bromide. Centrifuge for about 10 min and use the clear supernatant.

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: 40°

Flow rate: 3 mL/min

Injection volume: 50 μL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 1.0%2S (USP41)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of methscopolamine bromide (C₁₈H₂₄BrNO₄) in the portion of Tablets 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 = nominal concentration of methscopolamine bromide in the Sample solution (mg/mL)

Acceptance criteria: 93.0%–107.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: 0.1 N hydrochloric acid; 500 mL

Apparatus 2: 50 rpm

Time: 30 min

pH 3.0 phosphate buffer: 5.44 g/L of monobasic potassium phosphate in water, adjusted with 1 N phosphoric acid to a pH of 3.0

Mobile phase: Methanol and pH 3.0 phosphate buffer (1:3)

Standard solution: Solution of USP Methscopolamine Bromide RS in Medium having a known concentration similar to the one expected in the Sample solution

Sample solution: Use portions of the Sample solution that have been passed through a 0.45-μm PTFE filter.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 204 nm

Column: 4.6-mm × 15-cm; packing L1

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 25 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of methscopolamine bromide (C₁₈H₂₄BrNO₄) dissolved:

Result = (r_U/r_S)xC_S × V × (1/L) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

V = volume of the Medium, 500 mL

L = label claim (mg/Tablet)

Acceptance criteria: NLT 80% (Q) of the labeled amount of methscopolamine bromide (C H BrNO ) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Add the following:

Organic Impurities

Buffer, Solution A, Solution B, Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay.

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

System suitability solution: 1.0 mg/mL of USP Methscopolamine Bromide RS and 1.0 μg/mL of USP Scopolamine Hydrobromide RS in Diluent, from the Scopolamine hydrobromide solution

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

Standard solution: 2.0 μg/mL of USP Methscopolamine Bromide RS in Diluent from the Standard stock solution Sample solution

For Tablets that contain 2.5 mg of methscopolamine bromide: Place 20 Tablets in a 50-mL volumetric flask. Add 40–45 mL of Diluent, and sonicate for 30 min. Shake by mechanical means for 30 min, dilute with Diluent to volume, and mix. Centrifuge for about 10 min and use the clear supernatant.

For Tablets that contain 5 mg of methscopolamine bromide: Place 20 Tablets in a 100-mL volumetric flask. Add 80 mL of Diluent, and sonicate for 30 min. Shake by mechanical means for 30 min, dilute with Diluent to volume, and mix. Centrifuge for about 10 min and use the clear supernatant.

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 1 between methscopolamine and scopolamine

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of each impurity in the portion of Tablets taken:

Result = (r_U/r_S)x(C_S/C_U ) × (1/F) × 100

r_U = peak area of any impurity from the Sample solution

r_S = peak area of methscopolamine from the Standard solution

C_S = concentration of USP Methscopolamine Bromide RS in the Standard solution (μg/mL)

C_U = nominal concentration of methscopolamine bromide in the Sample solution (mg/mL)

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2.

Table 2

^a These impurities are controlled in the drug substance and are included in the table for identification only. They are not to be reported for the drug product and should not be included in the total impurities.

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

^c (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. 2S (USP41)

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at controlled room temperature.

Change to read:

USP Reference Standards 〈11〉

USP Methscopolamine Bromide RS

USP Scopolamine Hydrobromide RS2S (USP41)