Trospium Chloride

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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C₂₅H₃₀ClNO₃       427.96

Spiro [8-azoniabicyclo[3.2.1]octane-8,1′-pyrrolidinium], 3-[(hydroxydiphenylacetyl)oxy]-, chloride, (1R,3r,5S);

(1R,3r,5S)-3-[(Hydroxydiphenylacetyl)oxy]spiro[8-azoniabicyclo[3.2.1]octane-8,1′-pyrrolidinium] chloride CAS RN: 10405-02-4; UNII: 1E6682427E.

1 DEFINITION

Trospium Chloride contains NLT 98.0% and NMT 102.0% of trospium chloride (C₂₅H₃₀ClNO₃), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K _{(CN 1-MAY-2020)}

B. IDENTIFICATION TESTS GENERAL, Chloride (191): Meets the requirements

C. 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

Mobile phase: Acetonitrile, triethylamine, phosphoric acid, and water (300:1:3:700)

System suitability solution: 0.01 mg/mL of USP Trospium Chloride RS and 0.003 mg/mL each of USP Trospium Chloride Related Compound

A RS and USP Trospium Chloride Related Compound B RS in Mobile phase

Standard solution: 0.6 mg/ml. of USP Trospium Chloride RS in Mobile phase

Sample solution: 0.6 mg/mL of Trospium Chloride in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm x 25-cm; 5-µm packing L1. (Alternatively, a 4.6-mm x 25-cm column that contains 5-µm packing L7 may be used.)

Column temperature: 40°

Flow rate: 1 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 3 between trospium chloride related compound B and trospium, System suitability solution

Relative standard deviation: NMT 0.85% for six replicate injections, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of trospium chloride (C₂₅H₃₀ClNO₃) in the portion of Trospium Chloride 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 Trospium Chloride RS in the Standard solution (mg/mL)

C_u = concentration of Trospium Chloride in the Sample solution (mg/mL)

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

4 IMPURITIES

RESIDUE ON IGNITION (281)

Sample: 1 g

Acceptance criteria: NMT 0.1%

4.1 ORGANIC IMPURITIES

Mobile phase: Proceed as directed in the Assay.

Standard solution: 0.01 mg/mL of USP Trospium Chloride RS and 0.003 mg/mL each of USP Trospium Chloride Related Compound A RS and USP Trospium Chloride Related Compound B RS in Mobile phase

Sample solution: 3.0 mg/mL of Trospium Chloride in Mobile phase

Chromatographic system: Proceed as directed in the Assay, except for the following parameters.

Injection volume: 20 µL

Run time: NLT 3 times the retention time of trospium

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 3 between trospium chloride related compound B and trospium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of trospium chloride related compound A and trospium chloride related compound B in the portion of Trospium Chloride taken:

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

r_u = peak response of trospium chloride related compound A or trospium chloride related compound B from the Sample solution

r_s = peak response of trospium chloride related compound A or trospium chloride related compound B from the Standard solution

C_s = concentration of trospium chloride related compound A or trospium chloride related compound B in the Standard solution (mg/mL)

C_u = concentration of Trospium Chloride in the Sample solution (mg/mL)

Calculate the percentage of any other individual impurity in the portion of Trospium Chloride 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 trospium chloride related compound B from the Standard solution

C_s = concentration of USP Trospium Chloride Related Compound B RS in the Standard solution (mg/mL)

C_u = concentration of Trospium Chloride in the Sample solution (mg/mL)

Acceptance criteria: See Table 1. The reporting level for impurities is 0.05%.

Table 1

^a (1R,3r,5S)-8-Azabicyclo[3.2.1]octan-3-yl hydroxydiphenylacetate.

4.2 LIMIT OF TROSPIUM CHLORIDE RELATED COMPOUND C

Mobile phase: Acetonitrile, anhydrous formic acid, and water (20:0.2:80)

Diluent: Water

Standard solution: 0.1 mg/mL of USP Trospium Chloride Related Compound C RS in Diluent, using sonication to dissolve

Sample solution: 100.0 mg/mL of Trospium Chloride in Diluent, using sonication to dissolve. [NOTE-The solution is stable for 12 h.]

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: Refractive index

Column: 4.6-mm x 25-cm, 5-um packing L1

Column temperature: 40°

Flow rate: 0.8 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 5.0% for six replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of trospium chloride related compound C in the portion of Trospium Chloride taken:

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

r_u = peak response of trospium chloride related compound C from the Sample solution

r_s = peak response of trospium chloride related compound C from the Standard solution

C_s = concentration of USP Trospium Chloride Related Compound C RS in the Standard solution (mg/mL)

C_u = concentration of Trospium Chloride in the Sample solution (mg/mL)

Acceptance criteria: NMT 0.1%

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry the sample at 105° to constant weight.

Acceptance criteria: NMT 0.5%

pH 〈791〉

Sample solution: 10 mg/mL of Trospium Chloride in carbon dioxide-free water

Acceptance criteria: 5.0–7.0

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Protect from light. Store at room temperature.

USP Reference Standards 〈11〉

USP Trospium Chloride RS

USP Trospium Chloride Related Compound A RS

Benzilic acid.

C₁₄H₁₂O₃             228.24

USP Trospium Chloride Related Compound B RS

Nortropane benzilate;

(1R,3r,5S)-8-Azabicyclo[3.2.1]octan-3-yl hydroxydiphenylacetate.

C₂₁H₂₃NO₃         337.41

USP Trospium Chloride Related Compound C RS

Azoniaspironortropanol chloride;

(1R,3r,5S)-3-Hydroxyspiro[8-azoniabicyclo[3.2.1]octane-8,1′-pyrrolidinium] chloride, or (1R,3r,5S)-3-Hydroxyspiro[bicyclo[3.2.1]octane-8,1′- pyrrolidin]-1′-ium chloride.

C₁₁H₂₀ClNO       217.74