Trihexyphenidyl Hydrochloride Tablets

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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1 DEFINITION

Trihexyphenidyl Hydrochloride Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of trihexyphenidyl hydrochloride (C₂₀H₃₁NO · HCl).

2 IDENTIFICATION

A. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

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

3.1 Procedure

Solution A: 1.4 g/L of monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 4.0. Pass the solution through a suitable filter of 0.22-µm pore size.

Solution B: 0.5 mL of phosphoric acid in 1 L of acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Methanol and water (80:20)

Standard solution: 0.1 mg/mL of USP Trihexyphenidyl Hydrochloride RS in Diluent

Sample stock solution: Nominally 0.5 mg/mL of trihexyphenidyl hydrochloride prepared as follows. Transfer a suitable amount of Tablets (NLT 10), equivalent to 50 mg of trihexyphenidyl hydrochloride, to a 100-mL volumetric flask. Add 10 mL of 0.1 N hydrochloric acid and sonicate. Add another 80 mL of Solution B and sonicate again. Dilute with Solution B to volume. Centrifuge and use the supernatant.

Sample solution: Nominally 0.1 mg/mL of trihexyphenidyl hydrochloride in Diluent from the Sample stock solution

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 210 nm. For Identification test A, use a diode array detector in the range of 190–300 nm.
• Column: 2.1-mm × 10-cm; 2.6-µm packing L1
• Column temperature: 30°
• Flow rate: 0.3 mL/min
• Injection volume: 3.0 µL

System suitability

• Sample: Standard solution
• Suitability requirements
• Tailing factor: NMT 3.0
• Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of trihexyphenidyl hydrochloride (C₂₀H₃₁NO · HCl) in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of trihexyphenidyl from the Sample solution

rₛ = peak response of trihexyphenidyl from the Standard solution

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

Cᵤ = nominal concentration of trihexyphenidyl hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

4.1 Dissolution 〈711〉

Medium: pH 4.5 acetate buffer, prepared by mixing 3.0 g of sodium acetate and 1.7 mL of glacial acetic acid with water to obtain 1000 mL of solution with a pH of 4.50 ± 0.05; 900 mL

Apparatus 1: 100 rpm

Time: 45 min

Standard solution: A known concentration of USP Trihexyphenidyl Hydrochloride RS in Medium

Sample solution: Filtered portion of the solution under test

Bromocresol green solution: Dissolve 250 mg of bromocresol green in a mixture of 15 mL of water and 5 mL of 0.1 N sodium hydroxide, dilute with Medium to 500 mL, and mix. Extract 250 mL portions of this solution with two 100 mL portions of chloroform and discard the chloroform extracts.

Instrumental conditions

• Mode: UV-Vis
• Analytical wavelength: 415 nm
• Blank: Medium
• Analysis

Samples: Standard solution and Sample solution

Transfer an accurately measured volume of the Sample solution, estimated to contain about 50 µg of trihexyphenidyl hydrochloride, to a 50-mL centrifuge tube. Transfer an equal, accurately measured volume of the Standard solution to a second 50-mL centrifuge tube. Transfer an equal, accurately measured volume of Medium to a third 50-mL centrifuge tube to provide a Blank. Add 5 mL of the Bromocresol green solution and 10.0 mL of chloroform to each tube, insert the stoppers into the tubes, and shake vigorously for NLT 20 s. Centrifuge the mixtures to separate the layers. Aspirate and discard the upper aqueous layers. Filter each chloroform layer through a separate phase-separating filter paper. Determine the amount of trihexyphenidyl hydrochloride (C₂₀H₃₁NO · HCl) dissolved from the absorbance of the filtrate from the Sample solution in comparison with that from the Standard solution. The filtrate from the Blank is used to set the instrument.

Tolerances: NLT 75% (Q) of the labeled amount of trihexyphenidyl hydrochloride (C₂₀H₃₁NO · HCl) is dissolved.

4.2 Uniformity of Dosage Units 〈905〉

Meet the requirements

5 IMPURITIES

Change to read:

5.1 Organic Impurities

Solution A, Solution B, Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay.

System suitability solution: 0.1 mg/mL of USP Trihexyphenidyl Hydrochloride RS and 0.01 mg/mL of USP Trihexyphenidyl Related Compound A RS in Diluent

Standard solution: 0.001 mg/mL of USP Trihexyphenidyl Hydrochloride RS in Diluent

Sample solution: Nominally 1 mg/mL of trihexyphenidyl hydrochloride prepared as follows. Transfer a suitable amount of Tablets (NLT 10), equivalent to 100 mg of trihexyphenidyl hydrochloride, to a 100-mL volumetric flask. Add 10 mL of 0.1 N hydrochloric acid and sonicate. Add another 80 mL of Solution B and sonicate again. Dilute with Solution B to volume. Centrifuge and use the supernatant.

System suitability

• Samples: System suitability solution and Standard solution
• [Note-See Table 2 for relative retention times.]
• Suitability requirements
• Resolution: NLT 2.0, System suitability solution
• Relative standard deviation: NMT 2.0%, Standard solution
• Signal-to-noise ratio: NLT 50, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual unspecified degradation product in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of each unspecified degradation product from the Sample solution

rₛ = peak response of trihexyphenidyl from the Standard solution

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

Cᵤ = nominal concentration of trihexyphenidyl hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: See Table 2. Disregard any peak below 0.10%.

Table 2

ᵃ This impurity included for identification only and is not to be included in the calculation of total degradation products.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature.

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