Atomoxetine Capsules

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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Atomoxetine Capsules

1 DEFINITION

Atomoxetine Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of atomoxetine (C₁₇H₂₁NO).

2 IDENTIFICATION

Change to read:

A. ▲Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K or 197A▲ (CN 1-May-2020)

Standard: 6 mg/mL of USP Atomoxetine Hydrochloride RS in methanol. Dry the solution to a dry powder under an air or nitrogen purge for a minimum of 3 h.

Sample: Shake the contents of a sufficient number of Capsules, equivalent to about 60 mg of atomoxetine, with 10 mL of methanol. Centrifuge at 4000 rpm for 5 min. Evaporate the solution to a dry powder with the aid of a current of air or stream of nitrogen.

Acceptance criteria: The IR spectrum exhibits main bands at (±2) wavenumbers (cm⁻¹) 2955, 2855, 1599–1604, 1492, 1048, 1023, and 1010.

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

Procedure

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.

Mobile phase: Acetonitrile and Buffer (38:62)

System suitability solution: 0.1 mg/mL of atomoxetine (free base) from USP Atomoxetine Hydrochloride RS and 0.02 mg/mL of o-cresol in Mobile phase. Sonicate to aid in dissolution.

Standard solution: 0.1 mg/mL of atomoxetine (free base) from USP Atomoxetine Hydrochloride RS in Mobile phase. Sonicate to aid in dissolution.

Sample stock solution: From NLT 10 Capsules (including shells) prepared as follows. Add the intact Capsules to a suitable volumetric flask. Add Mobile phase to fill 65% of the final volume. Allow to stand for at least 10 min, then shake for 20 min. Dilute with Mobile phase to volume.

Sample solution: Nominally 0.1 mg/mL of atomoxetine, prepared by diluting a suitable volume of Sample stock solution with Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 220 nm

Column: 4.6-mm × 7.5-cm; 3.5-µm packing L7

Column temperature: 35°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

Run time: 1.7 times the retention time of atomoxetine

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for atomoxetine and o-cresol are 1.0 and 1.3, respectively.]

Suitability requirements

Resolution: NLT 3.5 between atomoxetine and o-cresol, System suitability solution

Tailing factor: NMT 2.0 for atomoxetine, System suitability solution

Relative standard deviation: NMT 1.0% for atomoxetine, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of atomoxetine (C₁₇H₂₁NO) in the portion of Capsules taken:

Result = (r_U / r_S) × (C_S / C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of atomoxetine in the Standard solution (mg/mL)

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

Acceptance criteria: 90.0%–110.0%

Atomoxetine-Capsules-ttt

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

Medium: 0.1 N hydrochloric acid; 1000 mL, deaerated, ▲if needed▲ (RB 1-May-2020)

Apparatus 2: 50 rpm, with ▲suitable▲ (RB 1-May-2020) sinker

Time: 30 min

Buffer and Mobile phase: Prepare as directed in the Assay.

Standard stock solution: 0.1 mg/mL of atomoxetine (free base) from USP Atomoxetine Hydrochloride RS in Medium. Sonicate to aid in dissolution.

Standard solution: Dilute the Standard stock solution with Medium to obtain a final concentration of (L/1000) mg/mL, where L is the Capsule label claim in mg.

Sample solution: Pass a portion of the solution under test through a suitable filter.

Chromatographic system: Proceed as directed in the Assay.

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.4%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of atomoxetine (C₁₇H₂₁NO) dissolved:

Result = (r_U / r_S) × (C_S / L) × V × 100 

r_U = peak response from the Sample solution

r_S= peak response from the Standard solution

C_S = concentration of atomoxetine in the Standard solution (mg/mL)

L = label claim (mg/Capsule)

V = volume of Medium (mL)

Tolerances: NLT 80% (Q) of the labeled amount of atomoxetine (C₁₇H₂₁NO) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

IMPURITIES

Organic Impurities

Buffer: Dissolve 4.9 g of sodium 1-decanesulfonate and 6.9 g of monobasic potassium phosphate in 1 L of water. Adjust with phosphoric acid to a pH of 3.1.

Mobile phase: Acetonitrile and Buffer (41:59)

Sensitivity solution: 0.1 µg/mL of atomoxetine in Mobile phase

System suitability solution: 1 mg/mL of atomoxetine containing atomoxetine N-amide prepared as follows. Weigh equal amounts of USP Atomoxetine Hydrochloride RS and Urea, and place in a volumetric flask. Add water to fill 10% of the final volume. Sonicate for 3 min. Place the flask in an 85° oven for 40 min. Allow the solution to cool to room temperature. Dilute with Mobile phase to volume. [Note—The oven temperature and time in the oven can be adjusted to give a suitable level of atomoxetine N-amide peak.]

Sample solution: 1 mg/mL of atomoxetine in Mobile phase, from the contents of NLT 5 Capsules prepared as follows. Transfer the Capsule contents to a suitable volumetric flask. Fill 50% of the final volume with Mobile phase. Swirl, and let stand for 15 min. Dilute with Mobile phase to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm × 15-cm; 3.5-µm packing L7

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 10 µL

Run time: 2.3 times the retention time of atomoxetine

System suitability

Samples: Sensitivity solution and System suitability solution

[Note—See Table 1 for the relative retention times.]

Suitability requirements

Resolution: NLT 2.6 between atomoxetine and atomoxetine N-amide, System suitability solution

Relative standard deviation: NMT 5%, Sensitivity solution

Analysis

Sample: Sample solution

Calculate the percentage of each individual impurity in the portion of Capsules taken:

Result = (r_U / r_S) × 100

r_U = peak response of each individual impurity from the Sample solution

r_S= sum of all the peak responses from the Sample solution

Acceptance criteria: See Table 1.

ᵃ (R)-N-Methyl-3-phenoxy-3-phenylpropan-1-amine.

ᵇ (R)-1-Methyl-1-[3-phenyl-3-(o-tolyloxy)propyl]urea.

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Atomoxetine Hydrochloride RS