Trihexyphenidyl Hydrochloride

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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C₂₀H₃₁NO·HCl  337.93

1-Piperidinepropanol, α-cyclohexyl-α-phenyl-, hydrochloride, (±)-;

(±)-α-Cyclohexyl-α-phenyl-1-piperidinepropanol hydrochloride CAS RN®: 52-49-3; UNII: AO61G82577.

1 DEFINITION

Trihexyphenidyl Hydrochloride contains NLT 98.0% and NMT 102.0% of trihexyphenidyl hydrochloride (C₂₀H₃₁NO·HCl), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

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

B. Identification Tests-General, Chloride 〈191〉

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

3.1 Procedure

Solution A: Add 0.2 mL of triethylamine in 200 mL of water and mix. Adjust with phosphoric acid to a pH of 4.0.

Mobile phase: Acetonitrile and Solution A (75:25)

Standard solution: 0.2 mg/mL of USP Trihexyphenidyl Hydrochloride RS in acetonitrile

Sample solution: 0.2 mg/mL of Trihexyphenidyl Hydrochloride in acetonitrile

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 210 nm
• Column: 3.9-mm × 15-cm; 5-µm packing L1
• Column temperature: 30°
• Flow rate: 1 mL/min
• Injection volume: 20 µL
• Run time: 3 times the retention time of trihexyphenidyl

System suitability

• Sample: Standard solution
• Suitability requirements
• Column efficiency: NLT 1300 theoretical plates
• Tailing factor: NMT 3.0
• Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of trihexyphenidyl hydrochloride (C₂₀H₃₁NO·HCl) in the portion of Trihexyphenidyl Hydrochloride 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 Trihexyphenidyl Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = concentration of Trihexyphenidyl Hydrochloride in the Sample solution (mg/mL)

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

4 IMPURITIES

4.1 Residue on Ignition 〈281〉: NMT 0.1%

4.2 Organic Impurities

Mobile phase and Chromatographic system: Proceed as directed in the Assay.

Standard stock solution: 0.02 mg/mL of USP Trihexyphenidyl Hydrochloride RS in Mobile phase

System suitability solution: 0.01 mg/mL of USP Trihexyphenidyl Related Compound A RS in Standard stock solution

Standard solution: 0.002 mg/mL of USP Trihexyphenidyl Hydrochloride RS from Standard stock solution in Mobile phase

Sample solution: 2 mg/mL of Trihexyphenidyl Hydrochloride in Mobile phase

System suitability

• Samples: System suitability solution and Standard solution
• [Note-See Table 1 for the relative retention times.]
• Suitability requirements
• Resolution: NLT 4.0 between trihexyphenidyl and trihexyphenidyl related compound A, System suitability solution
• Relative standard deviation: NMT 10.0%, Standard solution
• Signal-to-noise ratio: NLT 50, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Trihexyphenidyl Hydrochloride taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of each individual unspecified impurity from the Sample solution

rₛ = peak response of trihexyphenidyl hydrochloride from the Standard solution

Cₛ = concentration of USP Trihexyphenidyl Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = concentration of Trihexyphenidyl Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: See Table 1. Disregard any peaks below 0.02%.

Table 1

5 SPECIFIC TESTS

5.1 Loss on Drying 〈731〉

Analysis: Dry at 105° for 3 h.

Acceptance criteria: NMT 0.5%

5.2 pH 〈791〉

Sample solution: 10 mg/mL in water

Acceptance criteria: 5.2–6.2

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Trihexyphenidyl Hydrochloride RS

USP Trihexyphenidyl Related Compound A RS

1-Phenyl-3-(piperidin-1-yl)propan-1-one hydrochloride.

C₁₄H₁₉NO·HCl  253.77