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Printed by: USP NF Official Date: Official as of 01-May-2020 Document Type: USP @2024 USPC
Do Not Distribute DOI Ref: q7tz4 DOI: https://doi.org/10.31003/USPNF_M2432_02_01
1

rS = peak response from the Standard solution

Aripiprazole Orally Disintegrating CS = concentration of USP Aripiprazole RS in the
Tablets Standard solution (mg/mL)
CU = nominal concentration of aripiprazole in the
DEFINITION Sample solution (mg/mL)
Aripiprazole Orally Disintegrating Tablets contain NLT 90.0%
and NMT 110.0% of the labeled amount of aripiprazole Acceptance criteria: 90.0%–110.0%
(C23H27Cl2N3O2).
PERFORMANCE TESTS
IDENTIFICATION • DISINTEGRATION á701ñ: NMT 60 s
• DISSOLUTION á711ñ
Change to read: Medium: pH 4.0 sodium acetate trihydrate buffer (3.0 g/L
• A. ▲SPECTROSCOPIC IDENTIFICATION TESTS á197ñ, Infrared of sodium acetate prepared as follows. Transfer a suitable
Spectroscopy: 197A▲ (CN 1-May-2020) quantity of sodium acetate to a suitable container
• B. The retention time of the major peak of the Sample containing 90% of the final container volume of water.
solution corresponds to that of the Standard solution, as Adjust with glacial acetic acid to a pH of 4.0. Add water to
obtained in the Assay. the final volume.), degassed; 1000 mL
Apparatus 2: 75 rpm
ASSAY Time: 30 min
• PROCEDURE Mobile phase: Acetonitrile and 0.025 M hydrochloric acid
Solution A: 2.84 g/L of sodium sulfate in water (40:60)
Buffer: 3.48 g/L of dibasic potassium phosphate adjusted Standard solution: (L/1000) mg/mL of USP Aripiprazole RS
with phosphoric acid to a pH of 8.2 in Mobile phase where L is the label claim in mg/Tablet

al
Mobile phase: Acetonitrile and Buffer (50:50) Sample solution: Pass a portion of the solution under test
Diluent A: Acetonitrile, methanol, Solution A, and glacial through a suitable filter, discarding the first few mL.
acetic acid (33:11:56:1) Chromatographic system
Diluent B: Acetonitrile and 0.1 M hydrochloric acid (See Chromatography á621ñ, System Suitability.)
(20:80)
ci Mode: LC
System suitability solution: 0.01 mg/mL each of USP Detector: UV 225 nm
Aripiprazole RS and USP Aripiprazole Related Column: 4.6-mm × 15-cm; 5-µm packing L1
Compound G RS in Diluent A. Sonication and shaking may Flow rate: 1 mL/min
be used to aid in dissolution. Injection volume: 20 µL
Standard solution: 0.25 mg/mL of USP Aripiprazole RS in Run time: NLT 1.5 times the retention time of aripiprazole
ffi
Diluent B. Sonication may be used to aid in dissolution. System suitability
Sample solution: Nominally 0.2–0.3 mg/mL of aripiprazole Sample: Standard solution
from NLT 5 Orally Disintegrating Tablets prepared as Suitability requirements
follows. Transfer NLT 5 Orally Disintegrating Tablets to a Relative standard deviation: NMT 2.0%
suitable volumetric flask and dilute with Diluent B to NMT Analysis
75% of the final flask volume. Sonicate for 5 min and shake Samples: Standard solution and Sample solution
O

for 15 min. Dilute with Diluent B to volume. Pass the Calculate the percentage of the labeled amount of
resulting solution through a suitable filter and use the aripiprazole (C23H27Cl2N3O2) dissolved:
filtrate.
Chromatographic system Result = (rU/rS) × CS × V × (1/L) × 100
(See Chromatography á621ñ, System Suitability.)
Mode: LC rU = peak response from the Sample solution
Detector: UV 252 nm rS = peak response from the Standard solution
Column: 4.6-mm × 10-cm; 3.5-µm packing L1 CS = concentration of USP Aripiprazole RS in the
Flow rate: 1 mL/min Standard solution (mg/mL)
Injection volume: 10 µL V = volume of Medium, 1000 mL
Run time: NLT 1.4 times the retention time of aripiprazole L = label claim (mg/Tablet)
System suitability
Samples: System suitability solution and Standard solution Tolerances: NLT 80% (Q) of the labeled amount of
[NOTE—The relative retention times of aripiprazole aripiprazole (C23H27Cl2N3O2) is dissolved.
related compound G and aripiprazole are 0.74 and • UNIFORMITY OF DOSAGE UNITS á905ñ: Meet the
1.0, respectively.] requirements
Suitability requirements
Resolution: NLT 3.0 between aripiprazole related IMPURITIES
compound G and aripiprazole, System suitability solution • ORGANIC IMPURITIES
Tailing factor: NMT 1.5, Standard solution Solution A: Water and trifluoroacetic acid (100: 0.05)
Relative standard deviation: NMT 1.0%, Standard Solution B: Acetonitrile and trifluoroacetic acid (100: 0.05)
solution Solution C: 2.84 g/L of sodium sulfate in water
Analysis Mobile phase: See Table 1.
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of Table 1
aripiprazole (C23H27Cl2N3O2) in the portion of Orally Time Solution A Solution B
Disintegrating Tablets taken: (min) (%) (%)
0 90 10
Result = (rU/rS) × (CS/CU) × 100
20 70 30
rU = peak response from the Sample solution

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Printed on: Fri Jan 05 2024, 09:06:12 PM(EST) Status: Currently Official on 06-Jan-2024 DocId: GUID-28F6A917-A21C-4749-ACD0-6945D1F45859_2_en-US
Printed by: USP NF Official Date: Official as of 01-May-2020 Document Type: USP @2024 USPC
Do Not Distribute DOI Ref: q7tz4 DOI: https://doi.org/10.31003/USPNF_M2432_02_01
2

Table 1 (continued) F = relative response factor (see Table 2)

Time Solution A Solution B rU = peak response of aripiprazole from the Sample
(min) (%) (%) solution
40 42 58
Calculate the percentage of each degradation product in
50 10 90 the portion of Orally Disintegrating Tablets taken:
55 10 90
Result = (ri/rT) × (1/F) × 100
56 90 10
ri = peak response of each degradation product
60 90 10
from the Sample solution
rT = total peak response for individual impurities and
[NOTE—The gradient was established on an HPLC system aripiprazole from the Sample solution
with a dwell volume of approximately 1.0 mL.] F = relative response factor (see Table 2)
Diluent: Acetonitrile, methanol, Solution C, and glacial
acetic acid (33:11:56:1) Acceptance criteria: See Table 2. Disregard peaks less than
System suitability solution: 250 µg/mL of USP 0.05%.
Aripiprazole RS, and 0.5 µg/mL each of USP Aripiprazole
Related Compound F RS and USP Aripiprazole Related Table 2
Compound G RS in Diluent. Sonication may be used to aid Relative Relative Acceptance
in dissolution. Retention Response Criteria,
Sample solution: Nominally 0.2–0.3 mg/mL of aripiprazole Name Time Factor NMT (%)
from NLT 5 Orally Disintegrating Tablets prepared as

al
Aripiprazole related
follows. Transfer NLT 5 Orally Disintegrating Tablets to a compound G 0.96 0.77 0.3
suitable volumetric flask. Add about 70% of the total
Aripiprazole 1.0 — —
volume of Diluent. Sonicate for 10 min and shake for
10 min. Dilute with Diluent to volume. Pass the resulting Aripiprazole related
solution through a suitable filter and use the filtrate. compound F 1.03 1.0 0.3
Chromatographic system
(See Chromatography á621ñ, System Suitability.)
Mode: LC
ci Any individual
unspecified
degradation product — 1.0 0.2
Detector: UV 254 nm Total degradation
Column: 4.6-mm × 15-cm; 3-µm packing L1 products — — 1.0
ffi
Flow rate: 1 mL/min
Injection volume: 20 µL
ADDITIONAL REQUIREMENTS
System suitability
• PACKAGING AND STORAGE: Preserve in tight containers.
Sample: System suitability solution
Store at controlled room temperature.
[NOTE—See Table 2 for the relative retention times.]
• USP REFERENCE STANDARDS á11ñ
Suitability requirements
USP Aripiprazole RS
O

Resolution: NLT 4.0 between aripiprazole related

USP Aripiprazole Related Compound F RS
compound G and aripiprazole; NLT 1.5 between
4-(2,3-Dichlorophenyl)-1-[4-(2-oxo-1,2,3,4-
aripiprazole and aripiprazole related compound F
tetrahydroquinolin-7-yloxy)butyl]piperazine 1-oxide.
Analysis
C23H27Cl2N3O3 464.38
Sample: Sample solution
Calculate the total peak response for individual impurities USP Aripiprazole Related Compound G RS
and aripiprazole from the Sample solution: 7-{4-[4-(2,3-Dichlorophenyl)piperazin-1-yl]butoxy}
quinolin-2(1H)-one.
Result = Σ[ri × (1/F)] + rU C23H25Cl2N3O2 446.37

ri = peak response of each degradation product

from the Sample solution

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