Amphetamine Sulfate

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

(C₉H₁₃N)₂·H₂SO₄ 368.49

Benzeneethanamine, α-methyl-, sulfate (2:1), (±)-;

(±)-α-Methylphenethylamine sulfate (2:1)

CAS RN®: 60-13-9; UNII: 6DPV8NK46S.

1 DEFINITION

Amphetamine Sulfate contains NLT 98.0% and NMT 102.0% of (C₉H₁₃N)₂·H₂SO₄ on the dried basis.

2 IDENTIFICATION

Change to read:

A. ▲Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M▲ (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.

C. Identification Tests—General, Sulfate 〈191〉: Meets the requirements

Sample solution: 100 mg/mL

3 ASSAY

Procedure

Solution A: Add 5.0 mL of trifluoroacetic acid to 900 mL of water, adjust with ammonium hydroxide to a pH of 2.2 ± 0.1, and add 100 mL of acetonitrile.

Solution B: Use degassed acetonitrile.

Mobile phase: See the gradient table below.

Standard solution: 2.0 mg/mL of USP Dextroamphetamine Sulfate RS in Solution A

System suitability solution: Transfer 40 mL of the Standard solution to a 50-mL volumetric flask. Using a microliter syringe, add 1 µL each of USP Dextroamphetamine Related Compound A RS and USP Dextroamphetamine Related Compound B RS. Dilute with Standard solution to volume, and mix.

Sample solution: 2.0 mg/mL of Amphetamine Sulfate in Solution A

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 257 nm

Column: 4.6-mm × 15-cm; 5-µm packing L1

Column temperature: 40°C

Flow rate: 1.5 mL/min

Injection size: 20 µL

System suitability

Samples: Standard solution and System suitability solution

[Note—Identify the peaks by the relative retention times in Impurity Table 1 under Organic Impurities. Amphetamine and dextroamphetamine have exactly the same retention time.]

Suitability requirements

Resolution: NLT 3.0 between dextroamphetamine related compound A and dextroamphetamine related compound B, System suitability solution

Tailing factor: NMT 3.0, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of (C₉H₁₃N)₂·H₂SO₄ in the portion of Amphetamine Sulfate taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response for amphetamine sulfate from the Sample solution

rₛ = peak response for dextroamphetamine sulfate from the Standard solution

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

Cᵤ = concentration of Amphetamine Sulfate in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the dried basis

4 IMPURITIES

Inorganic Impurities

Residue on Ignition 〈281〉: NMT 0.2%

Organic Impurities

Procedure

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

Samples: Standard solution and Sample solution

[Note—Identify the impurities by the relative retention times in Impurity Table 1.]

Calculate the percentage of each impurity in the portion of Amphetamine Sulfate taken:

Result = (rᵢ/rₛ) × (Cₛ/Cᵢ) × (1/F) × 100

rᵢ = peak response for each impurity from the Sample solution

rₛ = peak response for dextroamphetamine from the Standard solution

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

Cᵢ = concentration of Amphetamine Sulfate in the Sample solution (mg/mL)

F = relative response factor (see Impurity Table 1)

Acceptance criteria

Individual impurities: See Impurity Table 1.

Total impurities: NMT 1.0%

5 SPECIFIC TESTS

Loss on Drying 〈731〉: Dry a sample at 105°C for 2 h: it loses NMT 1.0% of its weight.

Dextroamphetamine: A solution (20 mg/mL) is optically inactive.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers.

USP Reference Standards 〈11〉:

USP Dextroamphetamine Sulfate RS

USP Dextroamphetamine Related Compound A RS

1-Phenyl-2-propanol. C₉H₁₂O 136.20 CAS RN®: CAS-14898-87-4.

USP Dextroamphetamine Related Compound B RS

Phenyl acetone. C₉H₁₀O 134.18 CAS RN®: CAS-103-79-7.