Perphenazine

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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C₂₁H₂₆CIN₃OS 403.97

Piperazineethanol, 4-[3-(2-chloro-10H-phenothiazin-10-yl)propyl-];

4-[3-(2-Chlorophenothiazin-10-yl)propyl]-1-piperazineethanol CAS RN^®: 58-39-9; UNII: FTA7XXY4EZ.

1 DEFINITION

Perphenazine contains NLT 98.0% and NMT 102.0% of perphenazine (C₂₁H₂₆CIN₃OS), calculated on the dried basis. 26

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 Diluted sample solution corresponds to that of the Standard solution, as obtained in the test for Organic Impurities.

3 ASSAY

3.1 PROCEDURE

Sample solution: Dissolve 0.150 g of Perphenazine in 25 mL of glacial acetic acid.

Titrimetric system

(See Titrimetry (541).)

Mode: Direct titration

Titrant: 0.1 N perchloric acid VS

Endpoint detection: Potentiometric

3.2 Analysis

Sample: Sample solution

Titrate the Sample solution with Titrant. Carry out a blank titration.

Calculate the percentage of perphenazine (C₂₁H₂₆CIN₃OS) in the portion of Perphenazine taken:

Result = [(V - B) x N x F/W] x 100

V = Titrant volume consumed by the Sample (mL)

B = Titrant volume consumed by the blank (mL)

N = normality of the Titrant (meq/mL)

F = equivalent weight of perphenazine, 202.0 mg/meq

W = Sample weight (mg)

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

Prepare the solutions immediately before use. Carry out the test protected from light.

Solution A: Acetonitrile and 7 g/L of monobasic sodium phosphate dihydrate in water (35:65)

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

System suitability solution: 2 mg/mL of USP Perphenazine RS, 0.002 mg/mL of USP Perphenazine Sulfoxide RS, and 0.002 mg/mL of USP Perphenazine Related Compound B RS in Solution A

Standard solution: 0.002 mg/mL of USP Perphenazine RS in Solution A

Sample solution: 2 mg/mL of Perphenazine in Solution A

Diluted sample solution: 0.002 mg/mL of Perphenazine in Solution A from the Sample solution

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 245 nm

Column: 4.0-mm x 25-cm; 4-µm packing L7

Column temperature: 30°

Flow rate: 1.3 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution [NOTE-See Table 2 for relative retention times.]

Suitability requirements

Resolution: NLT 3.0 between perphenazine and perphenazine related compound B, System suitability solution

Tailing factor: NMT 2.5, Standard solution

Relative standard deviation: NMT 10.0%, Standard solution

Analysis

Samples: Standard solution, Sample solution, and Diluted sample solution. [NOTE-Diluted sample solution is used for Identification test B.]

Calculate the percentage of impurities in the portion of Perphenazine taken:

Result = (r_U/r_S) x (C_S/C_U) x (1/F) x 100

r_U = peak response for each impurity from the Sample solution

r_S = peak response of perphenazine from the Standard solution

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

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

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2.

Table 2

5 SPECIFIC TESTS

LOSS ON DRYING (731)

Analysis: Dry a sample in a vacuum at 65° for 4 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in tight, light-resistant containers.

6.2 USP REFERENCE STANDARDS (11)

USP Perphenazine RS

USP Perphenazine Related Compound B RS

2-{4-[3-(10H-Phenothiazin-10-yl)propyl]piperazin-1-yl}ethanol.

C₂₁H₂₇N₃OS 369.52

USP Perphenazine Sulfoxide RS

2-Chloro-10-{3-[4-(2-hydroxyethyl)piperazin-1-yl]propyl}-10H-phenothiazine 5-oxide.

C₂₁H₂₆CIN₃O₂S 419.97