Amphetamine Sulfate Tablets

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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Amphetamine Sulfate Tablets

To view the Notice from the Expert Committee that posted in conjunction with this accelerated revision

1 DEFINITION

Amphetamine Sulfate Tablets contain NLT 93.0% and NMT 107.0% of the labeled amount of amphetamine sulfate [(C₉H₁₃N)₂·H₂SO₄].

2 IDENTIFICATION

A. Melting Range or Temperature 〈741〉, Procedures: Class I

Sample: Nominally 50 mg of amphetamine sulfate from a suitable quantity of powdered Tablets

Analysis: Macerate the Sample with 10 mL of water for 30 min and filter into a small flask. To the filtrate add 3 mL of 1 N sodium hydroxide. Cool to 10°–15°, add 1 mL of a mixture of absolute ether and benzoyl chloride (2:1), insert the stopper, and shake well for 3 min. Filter the precipitate, wash with 15 mL of cold water, and recrystallize twice from diluted alcohol. Dry the residue at 80° for 2 h.

Acceptance criteria: The crystals of the benzoyl derivative of amphetamine melt between 131° and 135°.

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

Solution A: 14 mL of glacial acetic acid in 100 mL of water

Mobile phase: Dissolve 1.1 g of sodium 1-heptanesulfonate in 525 mL of water. Add 25 mL of Solution A and 450 mL of methanol. Adjust with glacial acetic acid to a pH of 3.3 ± 0.1.

Standard solution: 0.3 mg/mL of USP Dextroamphetamine Sulfate RS in 0.12 N phosphoric acid

Sample solution: Nominally 0.3 mg/mL of amphetamine sulfate from Tablets prepared as follows. Finely powder Tablets (NLT 20). Transfer a suitable amount of the powdered Tablets to a suitable volumetric flask. Add 80% of the flask volume of 0.12 N phosphoric acid, and sonicate for 15 min. Dilute with 0.12 N phosphoric acid to volume. Pass through a membrane filter of 0.5-µm pore size, discarding the first 20 mL of the filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm × 30-cm; 10-µm packing L1

Flow rate: 2 mL/min. [Note—Alternatively, a 4.6-mm × 25-cm column with 5-µm packing L1 may be used with a flow rate of 1 mL/min.]

Injection volume: 50 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 3

Relative standard deviation: NMT 1.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of amphetamine sulfate [(C₉H₁₃N)₂·H₂SO₄] in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of amphetamine from the Sample solution

rₛ = peak response of dextroamphetamine from the Standard solution

Cₛ = concentration of USP Dextroamphetamine Sulfate RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of amphetamine sulfate in the Sample solution (mg/mL)

Acceptance criteria: 93.0%–107.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Test 1

Medium: Water; 500 mL

Apparatus 1: 100 rpm

Time: 45 min

Solution A: 14 mL of glacial acetic acid in 100 mL of water

Mobile phase: 1.1 g of sodium 1-heptanesulfonate in 575 mL of water. Add 25 mL of Solution A, and 400 mL of methanol. Adjust with glacial acetic acid to a pH of 3.3 ± 0.1.

Standard solution: USP Dextroamphetamine Sulfate RS in Medium having a known concentration of USP Dextroamphetamine Sulfate RS similar to the concentration expected in the sample.

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

Chromatographic system

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm × 30-cm; 10-µm packing L1

Flow rate: 1 mL/min

Injection volume: 500 µL

System suitability

Sample: Standard solution

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of amphetamine sulfate [(C₉H₁₃N)₂·H₂SO₄] dissolved:

Result = (rᵤ/rₛ) × Cₛ × V × (1/L) × 100

rᵤ = peak response of amphetamine from the Sample solution

rₛ = peak response of dextroamphetamine from the Standard solution

Cₛ = concentration of USP Dextroamphetamine Sulfate RS in the Standard solution (mg/mL)

V = volume of Medium, 500 mL

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of amphetamine sulfate [(C₉H₁₃N)₂·H₂SO₄] is dissolved.

Test 2

If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Medium: Water; 500 mL, deaerated if necessary

Apparatus 1: 100 rpm

Time: 15 min

Solution A: 5 mL of trifluoroacetic acid in 950 mL of water. Adjust with ammonium hydroxide to a pH of 2.2. Add 50 mL of acetonitrile.

Solution B: Acetonitrile

Mobile phase: See Table 1 (below).

Table 1

Standard solution: (L/500) mg/mL of USP Dextroamphetamine Sulfate RS in Solution A, where L is the label claim in mg/Tablet

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

Chromatographic system

Mode: LC

Detector: UV 257 nm

Column: 4.6-mm × 15-cm; 2.6-μm packing L1

Column temperature: 40°C

Flow rate: 1 mL/min

Injection volume: 50 µL

System suitability

Sample: Standard solution

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Result = (rᵤ/rₛ) × Cₛ × V × (1/L) × 100

Tolerances: NLT 80% (Q) of amphetamine sulfate [(C₉H₁₃N)₂·H₂SO₄] is dissolved.

Test 3

If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.

Medium: Water; 500 mL

Apparatus 1: 100 rpm

Time: 20 min

Solution A: 14 mL of glacial acetic acid in 100 mL of water

Mobile phase: Dissolve 1.1 g of sodium 1-heptanesulfonate in 525 mL of water. Add 25 mL of Solution A and 450 mL of methanol. Adjust with glacial acetic acid to a pH of 3.3.

Diluent: 0.12 N phosphoric acid in water

Standard stock solution: 0.10 mg/mL of USP Dextroamphetamine Sulfate RS in Diluent. Sonicate to dissolve, if necessary.

Standard solution: (L/500) mg/mL of USP Dextroamphetamine Sulfate RS from the Standard stock solution in water, where L is the label claim in mg/Tablet

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, discarding an appropriate volume of filtrate so that a consistent result can be obtained.

Chromatographic system

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm × 30-cm; 10-μm packing L1

Column temperature: 35°C

Flow rate: 1.5 mL/min

Injection volume: 200 µL

Run time: NLT 2 times the retention time of amphetamine

System suitability

Sample: Standard solution

Tailing Factor: NMT 3.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Result = (rᵤ/rₛ) × Cₛ × V × (1/L) × 100

Tolerances: NLT 80% (Q) of amphetamine sulfate [(C₉H₁₃N)₂·H₂SO₄] is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 ADDITIONAL REQUIREMENTS

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

Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.

USP Reference Standards 〈11〉:

USP Dextroamphetamine Sulfate RS