Bethanechol 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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Bethanechol Chloride

C₇H₁₇ClN₂O₂ 196.68

1-Propanaminium, 2-[(aminocarbonyl)oxy]-N,N,N-trimethyl-, chloride, (±)-;

(±)-(2-Hydroxypropyl)trimethylammonium chloride carbamate

CAS RN®: 590-63-6; UNII: H4QBZ2LO84.

1 DEFINITION

Bethanechol Chloride contains NLT 98.0% and NMT 101.5% of bethanechol chloride (C₇H₁₇ClN₂O₂), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M (CN 1-May-2020)

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

C. Identification Tests—General, Chloride〈191〉: Meets the requirements

3 ASSAY

Procedure

Buffer: 29 mg/L of edetic acid in a solution prepared as follows. Transfer a portion of edetic acid to a suitable volumetric flask. Dissolve in water, using 50% of the final flask volume. Add 0.3 mL of nitric acid per L, and dilute with water to volume.

Mobile phase: Acetonitrile and Buffer (5:95)

System suitability solution: 0.1 mg/mL of bethanechol chloride in a solution prepared as follows. Transfer a portion of bethanechol chloride to a suitable volumetric flask. Add 4% of the final flask volume of 0.1 N sodium hydroxide, and allow to stand for 15 min. Add 4% of the final flask volume of 0.1 N hydrochloric acid. Dissolve in and dilute with Mobile phase to volume.

Standard solution: 0.1 mg/mL of USP Bethanechol Chloride RS in Mobile phase

Sample solution: 0.1 mg/mL of Bethanechol Chloride in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: Conductivity

Column: 3.9-mm × 15.0-cm; packing L55

Temperatures

Detector: 35°

Column: 30°

Flow rate: 1 mL/min

Injection volume: 25 µL

System suitability

Samples: System suitability solution and Standard solution

[Note—See Table 1 for the relative retention times.]

Suitability requirements

Resolution: NLT 0.8 between desacetyl methacholine and bethanechol chloride, System suitability solution

Tailing factor: NMT 3.5, Standard solution

Relative standard deviation: NMT 3.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of bethanechol chloride (C₇H₁₇ClN₂O₂) in the portion of Bethanechol Chloride taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response from the Sample solution

rₛ = peak response from the Standard solution

Cₛ = concentration of USP Bethanechol Chloride RS in the Standard solution (mg/mL)

Cᵤ = concentration of Bethanechol Chloride in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–101.5% on the dried basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Buffer: 0.48 g/L of methanesulfonic acid in water

Mobile phase: Acetonitrile and Buffer (5:95)

System suitability solution: 0.1 mg/mL of bethanechol chloride in a solution prepared as follows. Transfer a portion of bethanechol chloride to a suitable volumetric flask. Add 4% of the final flask volume of 0.1 N sodium hydroxide, and allow to stand for 15 min. Add 4% of the final flask volume of 0.1 N hydrochloric acid. Dissolve in and dilute with Mobile phase to volume.

Standard solution: 1 µg/mL of USP Bethanechol Chloride RS in Mobile phase

Sample solution: 0.1 mg/mL of Bethanechol Chloride in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: Conductivity

Column: 3.9-mm × 15.0-cm; packing L55

Temperatures

Detector: 35°

Column: 30°

Flow rate: 1 mL/min

Injection volume: 50 µL

System suitability

Samples: System suitability solution and Standard solution

[Note—See Table 1 for the relative retention times.]

Suitability requirements

Resolution: NLT 0.8 between desacetyl methacholine and bethanechol chloride, System suitability solution

Relative standard deviation: NMT 10.0% for bethanechol chloride, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Bethanechol Chloride taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × (1/F) × 100

rᵤ = peak response of any impurity from the Sample solution

rₛ = peak response of bethanechol chloride from the Standard solution

Cₛ = concentration of USP Bethanechol Chloride RS in the Standard solution (mg/mL)

Cᵤ = concentration of Bethanechol Chloride in the Sample solution (mg/mL)

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1.

¹ 2-Hydroxypropyltrimethyl ammonium chloride.

5 SPECIFIC TESTS

pH 〈791〉

Sample solution: 10 mg/mL of Bethanechol Chloride in water

Acceptance criteria: 5.5–6.5

Loss on Drying 〈731〉

Analysis: Dry at 105° for 2 h.

Acceptance criteria: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Bethanechol Chloride RS