Aripiprazole

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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C₂₃H₂₇CI₂N₃O₂  448.39

2(1H)-Quinolinone, 7-[4-[4-(2,3-dichlorophenyl)-1- piperazinyl]butoxy]-3,4-dihydro-;

7-[4-[4-(2,3-Dichlorophenyl)-1-piperazinyl]butoxy]-3,4-dihydrocarbostyril CAS RN^®: 129722-12-9; UNII: 82VFR53178.

1 DEFINITION

Aripiprazole contains NLT 98.0% and NMT 102.0% of aripiprazole (C₂₃H₂₇CI₂N₃O₂), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K (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.

3 ASSAY

3.1 PROCEDURE

Protect the solutions from light.

Diluent: Acetonitrile, methanol, water, and acetic acid (30:10:60:1)

Solution A: Acetonitrile and 0.05% trifluoroacetic acid (10:90)

Solution B: Acetonitrile and 0.05% trifluoroacetic acid (90:10)

Mobile phase: See Table 1.

Table 1

[NOTE-The gradient was established on an HPLC system with a dwell volume of approximately 650 µL.]

System suitability solution: 1 µg/mL each of USP Aripiprazole RS and USP Aripiprazole Related Compound F RS in Diluent

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

Sample solution: 0.1 mg/mL of Aripiprazole in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

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

Flow rate: 1.2 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for aripiprazole and aripiprazole related compound F are 1.0 and 1.1, respectively.]

Suitability requirements

Resolution: NLT 2.0 between aripiprazole and aripiprazole related compound F, System suitability solution

Tailing factor: NMT 1.5 for aripiprazole, System suitability solution

Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of aripiprazole (C₂₃H₂₇CI₂N₃O₂) in the portion of Aripiprazole taken:

Result = (r_S/r_U) × (C_S/C_U) × 100

r_S = peak area from the Sample solution

r_U = peak area from the Standard solution

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

C_U = concentration of Aripiprazole 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

Protect the solutions from light.

Diluent, Solution A, Solution B, Mobile phase, System suitability solution, Standard solution, Sample solution, Chromatographic system,

and System suitability: Proceed as directed in the Assay.

Analysis

Sample: Sample solution

Calculate the percentage of each impurity in the portion of Aripiprazole taken:

Result = (r_i/r_U) x (1/F) x 100

r_i = peak response of each impurity from the Sample solution

r_U = peak response of Aripiprazole from the Sample solution

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2.

Table 2

^a 7-(4-[4-(2,3-Dichlorophenyl)piperazin-1-yijputoxyquinolin-2(1H)-one.

^b 4-(2,3-Dichlorophenyl)-1-[4-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yloxy) butyl] Piperazine 1-oxide.

^c If possible from the manufacturing process.

^d 1,1'-(Ethane-1,1-diyl)bis 1-diyl)bis (2,3-dichloro-4-(4-[3,4-dihydroquinolin-2(1H)-one-7-yloxybutyl] piperazin-1-yl)benzene).

5 SPECIFIC TESTS

5.1 LOSS ON DRYING (731)

Analysis: Dry at 105° for 3 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in tight containers. Store at controlled room temperature.

6.2 USP REFERENCE STANDARDS (11)

USP Aripiprazole RS

USP Aripiprazole Related Compound F RS

4-(2,3-Dichlorophenyl)-1-[4-(2-oxo-1,2,3,4-tetrahydroquinolin-7-yloxy)butyl] piperazine 1-oxide.

C₂₃H₂₇CI₂N₃O₃  464.38