Scopolamine Hydrobromide

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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C₁₇H₂₁NO₄ .HBr. xH₂O 

Benzeneacetic acid, α-(hydroxymethyl)-, 9-methyl-3-oxa-9-azatricyclo[3.3.1.0.2,4]non-7-yl ester, hydrobromide,hydrate, (USP 1-Dec-2021) [7(S)- (1α,2β,4β,5α,7β)]-; 

6β,7β-Epoxy-1αH,5αH-tropan-3α-ol (−)-tropate (ester) hydrobromidehydrate; 

(1R,2R,4S,5S,7s)-9-Methyl-3-oxa-9-azatricyclo[3.3.1.0.2,4]nonan-7-yl (S)-3-hydroxy-2-phenylpropanoate hydrobromide hydrate (USP 1-Dec-2021) Anhydrous 384.27 CAS RN®: 114-49-8; UNII: R3K67DRL3J. 

1 DEFINITION 

Scopolamine Hydrobromide contains NLT 98.0% and NMT 102.0% of scopolamine hydrobromide (C₁₇H₂₁NO₄ .HBr), calculated on the anhydrous basis. 

[Caution—Handle scopolamine hydrobromide with exceptional care, because it is highly potent.] 

2 IDENTIFICATION 

Change to read: 

A.Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K 

Sample: (USP 1-Dec-2021) Dissolve 3 mg in 1 mL of alcohol, and evaporate the solution on a steam bath to dryness. Dissolve the residue in 0.5 mL of chloroform, add 200 mg of potassium bromide previously dried at 105° for 30 min, and stir frequently for 5 min. Allow the chloroform to evaporate to dryness, and stir frequently to obtain a owing powder residue. Dry the residue as directed in the test for Water Determination, (USP 1-Dec-2021) and then immediately compress the residue to a disk. 

Standard solution: Proceed as directed in the Sample using USP Scopolamine Hydrobromide RS. (USP 1-Dec-2021) Acceptance criteria: Meets the requirements 

A. Sample solution: 50 mg/mL of Scopolamine Hydrobromide in water 

Analysis: To 1 mL of the Sample solution add a few drops of chlorine TS, and shake the mixture with 1 mL of chloroform. Acceptance criteria: A brownish color forms in the chloroform layer. 

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

3 ASSAY 

Procedure 

Buffer solution: 7.0 g/L of monobasic potassium phosphate in water. Adjust with 0.05 M phosphoric acid to a pH of 3.3. Solution A: Dissolve 3.5 g of sodium dodecyl sulfate in 606 mL of Buffer solution. Add 320 mL of acetonitrile and mix. Solution B: Acetonitrile 

Mobile phase: See Table 1. 

Table 1 

Standard solution: 0.2 mg/mL of USP Scopolamine Hydrobromide RS in Solution A 

Sample solution: 0.2 mg/mL of Scopolamine Hydrobromide in Solution A 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 210 nm 

Column: 4.6-mm × 10-cm; 3-µm packing L1 

Flow rate: 1 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 scopolamine hydrobromide (C₁₇H₂₁NO₄ . HBr) in the portion of Scopolamine Hydrobromide taken: 

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response of scopolamine from the Sample solution 

r_S = peak response of scopolamine from the Standard solution  

C_S = concentration of USP Scopolamine Hydrobromide RS in the Standard solution (mg/mL)  

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

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

4 IMPURITIES 

Residue on Ignition 〈281〉 

Sample: 1 g 

Acceptance criteria: NMT 0.1% 

Organic Impurities 

Buffer solution, Solution A, Solution B, Mobile phase, and Chromatographic system: Proceed as directed in the Assay. System suitability solution: 0.2 mg/mL of USP Scopolamine Hydrobromide RS and 0.001 mg/mL of USP Norscopolamine RS in Solution A Standard solution: 0.002 mg/mL of USP Scopolamine Hydrobromide RS in Solution A 

Sample solution: 2.0 mg/mL of Scopolamine Hydrobromide in Solution A 

System suitability 

Samples: System suitability solution and Standard solution 

Suitability requirements 

Resolution: NLT 2.0 between the norscopolamine and scopolamine peaks, System suitability solution 

Relative standard deviation: NMT 5.0%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of each individual impurity in the portion of Scopolamine Hydrobromide taken: 

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

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

r_S = peak response of scopolamine from the Standard solution 

C_S = concentration of USP Scopolamine Hydrobromide RS in the Standard solution (mg/mL)  

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

F = relative response factor (see Table 2) 

Acceptance criteria: See Table 2. The reporting threshold is 0.05%. Disregard any peak due to the bromide ion at a relative retention time of 0.1 that appears close to the solvent peak. 

Table 2 

a 3-Hydroxy-2-phenylpropanoic acid. 

b (1R,3r,5S)-8-Methyl-8-azabicyclo[3.2.1]octan-3-yl (S)-3-hydroxy-2-phenylpropanoate. 

c (1R,2R,4S,5S,7s)-9-Methyl-3-oxa-9-azatricyclo[3.3.1.02,4]nonan-7-yl 2-phenylacrylate. 

d (1R,3r,5S)-8-Methyl-8-azabicyclo[3.2.1]octan-3-yl 2-phenylacrylate. 

5 SPECIFIC TESTS 

Optical Rotation 〈781S〉, Procedures, Specific Rotation 

Sample solution: 50 mg/mL of anhydrous Scopolamine Hydrobromide in water 

Acceptance criteria: −24° to −26° 

pH 〈791〉 

Sample solution: 50 mg/mL of Scopolamine Hydrobromide in water 

Acceptance criteria: 4.0–5.5 

Water Determination 〈921〉, Method III 

Analysis: Dry in two stages (see Loss on Drying 〈731〉): first at 80° for 2 h, and then at 105° for an additional 3 h. 

Acceptance criteria: NMT 13.0% 

6 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in tight, light-resistant containers. 

USP Reference Standards 〈11〉 

USP Norscopolamine RS 

(1R,2R,4S,5S,7s)-3-Oxa-9-azatricyclo[3.3.1.02,4]nonan-7-yl (S)-3-hydroxy-2-phenylpropanoate. 

C₁₆H₁₉NO₄ 289.33 

USP Scopolamine Hydrobromide RS