Aripiprazole
C23H27Cl2N3O2 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 [129722-12-9]; UNII: 82VFR53I78.
DEFINITION
Aripiprazole contains NLT 98.0% and NMT 102.0% of aripiprazole (C23H27Cl2N3O2), calculated on the dried basis.
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.
ASSAY
• PROCEDURE
Protect the solutions from light.
Diluent: Acetonitrile, methanol, water, and acetic acid (30:10:60:1)
Solution A: Acetonitrile and 0.05% triuoroacetic acid (10:90)
Solution B: Acetonitrile and 0.05% triuoroacetic acid (90:10)
Mobile phase: See Table 1.
Table 1
Time (min) Solution A (%) Solution B (%)
0 80 20
2 80 20
10 65 35
20 10 90
25 10 90
26 80 20
35 80 20
[ 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 (C23H27Cl2N3O2) in the portion of Aripiprazole taken:
Result = (ru /rs ) × (Cs /Cu ) × 100
ru = peak area from the Sample solution
rs = peak area from the Standard solution
Cs = concentration of USP Aripiprazole RS in the Standard solution (mg/mL)
Cu = concentration of Aripiprazole in the Sample solution (mg/mL)
Acceptance criteria: 98.0%-102.0% on the dried basis
IMPURITIES
• RESIDUE ON IGNITION <281>: NMT 0.1%
• 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 = (ri /ru ) × (1/F) × 100
ri = peak response of each impurity from the Sample solution
ru = peak response of Aripiprazole from the Sample solution
F = relative response factor (see Table 2)
Acceptance criteria: See Table 2.
Table 2
Name Relative Retention Time Relative Response Factor Acceptance Criteria, NMT (%)
Aripiprazole related compound G a 0.9 0.72 0.10
Aripiprazole 1.0- -
Aripiprazole related compound F bc 1.1 1.0 0.10
Aripiprazole 4,4′-dimer d 1.3 1.0 0.10
Any other individual impurity – 1.0 0.10
Total impurities – - 0.50
a 7-{4-[4-(2,3-Dichlorophenyl)piperazin-1-yl]butoxy}quinolin-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(2,3-dichloro-4-{4-[3,4-dihydroquinolin-2(1H)-one-7-yloxybutyl]piperazin-1-yl}benzene).
SPECIFIC TESTS
• LOSS ON DRYING <731>
Analysis: Dry at 105℃ for 3 h.
Acceptance criteria: NMT 0.5%
ADDITIONAL REQUIREMENTS
• PACKAGING AND STORAGE: Preserve in tight containers. Store at controlled room temperature.
• 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.
C23H27Cl2N3O3 464.38
Contact: Dr. Alvin Huang
Mobile/Wechat/WhatsApp: +86-15026746401
E-Mail: alvin@ruifuchem.com