Printed on: Sat Jun 26 2021, 07:16:54 AM Official Status: Currently Official on 26-Jun-2021 DocId: 1_GUID-5C18BF39-709E-43C6-8BB3-0AB712ACA46F_3_en-US
(EST)
Printed by: Nguyen Nhan Official Date: Official as of 01-May-2020 Document Type: USP @2021 USPC
1
Calculate the percentage of the labeled amount of
Atomoxetine Capsules atomoxetine (C17H21NO) in the portion of Capsules taken:
DEFINITION
Atomoxetine Capsules contain NLT 90.0% and NMT 110.0% Result = (rU/rS) × (CS/CU) × 100
of the labeled amount of atomoxetine (C17H21NO).
rU = peak response from the Sample solution
IDENTIFICATION rS = peak response from the Standard solution
CS = concentration of atomoxetine in the Standard
Change to read: solution (mg/mL)
• A. ▲SPECTROSCOPIC IDENTIFICATION TESTS á197ñ, Infrared CU = nominal concentration of atomoxetine in the
Spectroscopy: 197K or 197A▲ (CN 1-May-2020) Sample solution (mg/mL)
Standard: 6 mg/mL of USP Atomoxetine Hydrochloride RS Acceptance criteria: 90.0%–110.0%
in methanol. Dry the solution to a dry powder under an air
or nitrogen purge for a minimum of 3 h. PERFORMANCE TESTS
Sample: Shake the contents of a sufficient number of
Capsules, equivalent to about 60 mg of atomoxetine, with Change to read:
10 mL of methanol. Centrifuge at 4000 rpm for 5 min.
• DISSOLUTION á711ñ
Evaporate the solution to a dry powder with the aid of a
Medium: 0.1 N hydrochloric acid; 1000 mL, deaerated, ▲if
current of air or stream of nitrogen.
needed▲ (RB 1-May-2020)
Acceptance criteria: The IR spectrum exhibits main bands
at (±2) wavenumbers (cm−1) 2955, 2855, 1599–1604, Apparatus 2: 50 rpm, with ▲suitable▲ (RB 1-May-2020) sinker
1492, 1048, 1023, and 1010. Time: 30 min
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• B. The retention time of the major peak of the Sample Buffer and Mobile phase: Prepare as directed in the Assay.
solution corresponds to that of the Standard solution, as Standard stock solution: 0.1 mg/mL of atomoxetine (free
obtained in the Assay. base) from USP Atomoxetine Hydrochloride RS in Medium.
Sonicate to aid in dissolution.
ASSAY Standard solution: Dilute the Standard stock solution with
• PROCEDURE Medium to obtain a final concentration of (L/1000) mg/mL,
Buffer: 5.8 g/L of monobasic potassium phosphate in water.
To each liter of this solution add 3.0 mL of triethylamine,
and adjust with phosphoric acid to a pH of 2.5.
ci where L is the Capsule label claim in mg.
Sample solution: Pass a portion of the solution under test
through a suitable filter.
Mobile phase: Acetonitrile and Buffer (38:62) Chromatographic system: Proceed as directed in the
System suitability solution: 0.1 mg/mL of atomoxetine Assay.
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(free base) from USP Atomoxetine Hydrochloride RS and System suitability
0.02 mg/mL of o-cresol in Mobile phase. Sonicate to aid in Sample: Standard solution
dissolution. Suitability requirements
Standard solution: 0.1 mg/mL of atomoxetine (free base) Tailing factor: NMT 2.0
from USP Atomoxetine Hydrochloride RS in Mobile phase. Relative standard deviation: NMT 1.4%
Sonicate to aid in dissolution. Analysis
O
Sample stock solution: From NLT 10 Capsules (including Samples: Standard solution and Sample solution
shells) prepared as follows. Add the intact Capsules to a Calculate the percentage of the labeled amount of
suitable volumetric flask. Add Mobile phase to fill 65% of the atomoxetine (C17H21NO) dissolved:
final volume. Allow to stand for at least 10 min, then shake
for 20 min. Dilute with Mobile phase to volume. Result = (rU/rS) × (CS/L) × V × 100
Sample solution: Nominally 0.1 mg/mL of atomoxetine,
prepared by diluting a suitable volume of Sample stock rU = peak response from the Sample solution
solution with Mobile phase rS = peak response from the Standard solution
Chromatographic system CS = concentration of atomoxetine in the Standard
(See Chromatography á621ñ, System Suitability.) solution (mg/mL)
Mode: LC L = label claim (mg/Capsule)
Detector: UV 220 nm V = volume of Medium (mL)
Column: 4.6-mm × 7.5-cm; 3.5-µm packing L7
Column temperature: 35° Tolerances: NLT 80% (Q) of the labeled amount of
Flow rate: 1.5 mL/min atomoxetine (C17H21NO) is dissolved.
Injection volume: 10 µL • UNIFORMITY OF DOSAGE UNITS á905ñ: Meet the
Run time: 1.7 times the retention time of atomoxetine requirements
System suitability
Samples: System suitability solution and Standard solution IMPURITIES
[NOTE—The relative retention times for atomoxetine • ORGANIC IMPURITIES
and o-cresol are 1.0 and 1.3, respectively.] Buffer: Dissolve 4.9 g of sodium 1-decanesulfonate and
Suitability requirements 6.9 g of monobasic potassium phosphate in 1 L of water.
Resolution: NLT 3.5 between atomoxetine and o-cresol, Adjust with phosphoric acid to a pH of 3.1.
System suitability solution Mobile phase: Acetonitrile and Buffer (41:59)
Tailing factor: NMT 2.0 for atomoxetine, System Sensitivity solution: 0.1 µg/mL of atomoxetine in Mobile
suitability solution phase
Relative standard deviation: NMT 1.0% for System suitability solution: 1 mg/mL of atomoxetine
atomoxetine, Standard solution containing atomoxetine N-amide prepared as follows.
Analysis Weigh equal amounts of USP Atomoxetine
Samples: Standard solution and Sample solution Hydrochloride RS and urea, and place in a volumetric flask.
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Add water to fill 10% of the final volume. Sonicate for Result = (rU/rT) × 100
3 min. Place the flask in an 85° oven for 40 min. Allow the
solution to cool to room temperature. Dilute with rU = peak response of each individual impurity from
Mobile phase to volume. [NOTE—The oven temperature and the Sample solution
time in the oven can be adjusted to give a suitable level of rT = sum of all the peak responses from the Sample
atomoxetine N-amide peak.] solution
Sample solution: 1 mg/mL of atomoxetine in Mobile phase,
from the contents of NLT 5 Capsules prepared as follows. Acceptance criteria: See Table 1.
Transfer the Capsule contents to a suitable volumetric flask.
Fill 50% of the final volume with Mobile phase. Swirl, and Table 1
let stand for 15 min. Dilute with Mobile phase to volume. Relative Acceptance
Chromatographic system Retention Criteria,
(See Chromatography á621ñ, System Suitability.) Name Time NMT (%)
Mode: LC Desmethyl atomoxetinea 0.76 0.3
Detector: UV 215 nm
Column: 4.6-mm × 15-cm; 3.5-µm packing L7 Atomoxetine 1.0 —
Column temperature: 30° Atomoxetine
Flow rate: 1 mL/min N-amideb 1.2 0.2
Injection volume: 10 µL Any individual
Run time: 2.3 times the retention time of atomoxetine unspecified degradation prod- —
System suitability uct 0.2
Samples: Sensitivity solution and System suitability solution
Total impurities — 1.0
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[NOTE—See Table 1 for the relative retention times.]
Suitability requirements a (R)-N-Methyl-3-phenoxy-3-phenylpropan-1-amine.
Resolution: NLT 2.6 between atomoxetine and b (R)-1-Methyl-1-[3-phenyl-3-(o-tolyloxy)propyl]urea.
atomoxetine N-amide, System suitability solution
Relative standard deviation: NMT 5%, Sensitivity ADDITIONAL REQUIREMENTS
solution • PACKAGING AND STORAGE: Preserve in well-closed
Analysis
Sample: Sample solution
Calculate the percentage of each individual impurity in the
ci containers. Store at controlled room temperature.
• USP REFERENCE STANDARDS á11ñ
USP Atomoxetine Hydrochloride RS
portion of Capsules taken:
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