Benztropine Mesylate

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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C₂₁H₂₅NO · CH₄O₃S           403.54

8-Azabicyclo[3.2.1]octane, 3-(diphenylmethoxy)-N-methyl-, endo-, methanesulfonate;

3α-(Diphenylmethoxy)-1αH,5αH-tropane methanesulfonate;

(1R,3r,5S)-3-(Benzhydryloxy)-8-methyl-8-azabicyclo[3.2.1]octane methanesulfonate CAS RN: 132-17-2.

1 DEFINITION

Benztropine Mesylate contains NLT 98.0% and NMT 102.0% of benztropine mesylate (C₂H₂NO CHO₂S), calculated on the dried basis.

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K or 197A

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

3 ASSAY

PROCEDURE

Solution A: 2.7 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 3.2.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (30:70)

System suitability solution: 500 µg/mL of USP Benztropine Mesylate RS and 5 µg/mL of USP Benztropine Related Compound A RS in Diluent

Standard solution: 500 µg/mL of USP Benztropine Mesylate RS in Diluent

Sample solution: 500 µg/mL of Benztropine Mesylate in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 2.1-mm × 15-cm; 1.7-µm packing L43. [Note—A guard column with similar packing may be used.]

Flow rate: 0.3 mL/min

Injection volume: 2 µL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for benztropine related compound A and benztropine are 0.9 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 1.3 between benztropine related compound A and benztropine, System suitability solution

Tailing factor: NMT 3.0, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of benztropine mesylate (C₂₁H₂₅NO · CH₄O₃S) in the portion of Benztropine Mesylate taken:

Result = (r_u /r_s ) × (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 Benztropine Mesylate RS in the Standard solution (µg/mL)

C_u = concentration of Benztropine Mesylate in the Sample solution (µg/mL)

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

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Change to read:

Organic Impurities

Solution A, Solution B, Diluent, System suitability solution, Sample solution, and Chromatographic system: Proceed as directed in the

Assay.

Mobile phase: See Table 2.

Table 2

Sensitivity solution: 0.25 µg/mL of USP Benztropine Mesylate RS in Diluent

Standard solution: 0.5 µg/mL of USP Benztropine Mesylate RS and 1 µg/mL each of USP Benztropine Related Compound A RS, USP Benzhydrol RS, and USP Benzophenone RS in Diluent

System suitability

Samples: System suitability solution, Sensitivity solution, and Standard solution

[NOTE-See Table 3 for the relative retention times.]

Suitability requirements

Resolution: NLT 1.3 between benztropine related compound A and benztropine, System suitability solution

Relative standard deviation: NMT 5.0% for benztropine, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of benztropine related compound A, benzhydrol, or benzophenone in the portion of Benztropine Mesylate taken:

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

r_u = peak response of benztropine related compound A, benzhydrol, or benzophenone from the Sample solution

r_s = peak response of the corresponding Reference Standard from the Standard solution

C_s = concentration of the corresponding Reference Standard in the Standard solution (µg/mL)

C_u = concentration of Benztropine Mesylate in the Sample solution (µg/mL)

Calculate the percentage of diphenylmethane or any individual unspecied impurity in the portion of Benztropine Mesylate taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (1/F) × 100

r_u = peak response of diphenylmethane or any individual unspecied impurity from the Sample solution

r_s = peak response of benztropine from the Standard solution

C_s = concentration of USP Benztropine Mesylate RS in the Standard solution (µg/mL)

C_u = concentration of Benztropine Mesylate in the Sample solution (µg/mL)

F = relative response factor (see Table 3)

Acceptance criteria: See Table 3. The reporting threshold is 0.05%.

Table 3

5 SPECIFIC TESTS

LOSS ON DRYING (731).

Analysis: Dry at 105° for 2 h.

Acceptance criteria: NMT 5.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

USP REFERENCE STANDARDS (11)

USP Benzhydrol RS

Diphenylmethanol.

C₁₃H₁₂O                 184.24

USP Benzophenone RS

Benzophenone; also known as Diphenylmethanone.

C₁₃H₁₀O                 182.22

USP Benztropine Mesylate RS

USP Benztropine Related Compound A RS

(1R,3r,5S)-3-(Benzhydryloxy)-8-azabicyclo[3.2.1]octane hydrochloride.

C₂₀H₂₃NO · HCl      329.87