Pimozide 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

Pimozide Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of pimozide (C₂₈H₂₉F₂N₃O).

2 IDENTIFICATION

Change to read:

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

Sample: Grind an appropriate number of Tablets to prepare a 1-mg/mL solution of pimozide in dichloromethane. Shake the solution for 5 min, and pass through a suitable filter. Evaporate the filtrate to dryness under reduced pressure. Use the dried residue.

Acceptance criteria: Meet the requirements

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

Protect all pimozide solutions from light.

Solution A: 2.5 g/L of ammonium acetate and 8.5 g/L of tetrabutylammonium hydrogen sulfate in water

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

System suitability solution: 0.04 mg/mL of USP Pimozide RS and 0.02 mg/mL of USP Mebendazole RS in methanol Standard solution: 0.4 mg/mL of USP Pimozide RS in methanol

Sample solution: Nominally 0.4 mg/mL of pimozide prepared as follows. Transfer a suitable number of powdered Tablets (NLT 20) to a suitable volumetric flask. Add about 70% of the ask volume of methanol, and mechanically shake for 30 min. Dilute with methanol to volume, and mix well with the aid of sonication for 10 min. Centrifuge, and pass a portion of the supernatant through a suitable filter of 0.45-µm pore size.

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 4.6-mm × 10-cm; 3-µm packing L1

Flow rate: 2 mL/min

Injection volume: 10 µL

3.2 System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for mebendazole and pimozide are 0.88 and 1.0, respectively.] Suitability requirements

Resolution: NLT 5.0 between the pimozide and mebendazole peaks, System suitability solution Relative standard deviation: NMT 2.0% for pimozide, Standard solution

3.3 Analysis

3.4 Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of pimozide (C₂₈H₂₉F₂N₃O) in the portion of Tablets taken: 

Result = ((r_U /r_S) × (C_S /C_U ) × 100

r_U = peak response of pimozide from the Sample solution

r_S = peak response of pimozide from the Standard solution

C_S = concentration of USP Pimozide RS in the Standard solution (mg/mL)

C_U = nominal concentration of pimozide in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Medium: 0.01 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Buffer: 5 g/L of ammonium acetate in water. Adjust with glacial acetic acid to a pH of 4.5.

Mobile phase: Acetonitrile and Buffer (40:60)

Standard solution: (L/900) mg/mL of USP Pimozide RS in Mobile phase, where L is the label claim of pimozide in mg/Tablet Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.

4.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 3.0-mm × 25-cm; 5-µm packing L1

Flow rate: 0.8 mL/min

Injection volume: 100 µL

Run time: 2.5 times the retention time of pimozide

4.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

4.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of pimozide (C₂₈H₂₉F₂N₃O) dissolved:

Result = ((r_U /r_S) × C_S × V × (1/L) × 100

r_U = peak response of pimozide from the Sample solution

r_S = peak response of pimozide from the Standard solution

C_S = concentration of USP Pimozide RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of pimozide (C₂₈H₂₉F₂N₃O) is dissolved.

Uniformity of Dosage Units 〈905〉, Content Uniformity: Meet the requirements

5 IMPURITIES

Organic Impurities

Protect all pimozide solutions from light.

Solution A, Solution B, Mobile phase, System suitability solution, and Chromatographic system: Proceed as directed in the Assay. Standard solution: 0.01 mg/mL of USP Pimozide RS in methanol

Sample solution: Nominally 2 mg/mL of pimozide prepared as follows. Transfer a suitable number of powdered Tablets (NLT 20) to a suitable volumetric ask. Add about 70% of the ask volume of methanol, and mechanically shake for 30 min. Dilute with methanol to volume, and mix well with the aid of sonication for 10 min. Centrifuge, and pass a portion of the supernatant through a suitable filter of 0.45-µm pore size.

5.1 System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for mebendazole and pimozide are 0.88 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 5.0 between pimozide and mebendazole, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

5.2 Analysis

Samples: Standard solution and Sample solution

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

Result = (r_U /r_S) × (C_S/C_U ) × 100

r_U = peak response of any individual unspecified degradation product from the Sample solution

r_S = peak response of pimozide from the Standard solution

C_S = concentration of USP Pimozide RS in the Standard solution (mg/mL)

C_U = nominal concentration of pimozide in the Sample solution (mg/mL)

5.3 Acceptance criteria

Any individual degradation product: NMT 1.0%

Total degradation products: NMT 2.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Mebendazole RS

USP Pimozide RS