Benzphetamine Hydrochloride 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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1 DEFINITION

Benzphetamine Hydrochloride Tablets contain NLT 93.0% and NMT 105.0% of the labeled amount of benzphetamine hydrochloride (C₁₇H₂₁N · HCl).

2 IDENTIFICATION

A. The retention time of the benzphetamine peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. The UV spectrum of the benzphetamine peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Buffer: Dissolve 2.76 g of monobasic sodium phosphate dihydrate in 1000 mL of water. Add 1.0 mL of triethylamine and adjust with phosphoric acid to a pH of 4.5.

Solution A: Acetonitrile and Buffer (10:90)

Solution B: Acetonitrile and water (80:20)

Mobile phase: Solution A and Solution B (65:35)

Diluent: Methanol and water (50:50)

Standard solution: 0.2 mg/mL of USP Benzphetamine Hydrochloride RS in Diluent. Sonicate to dissolve if necessary.

Sample solution: Nominally 0.2 mg/mL of benzphetamine hydrochloride in Diluent, prepared as follows. Transfer an adequate amount of benzphetamine hydrochloride from NLT 20 finely powdered Tablets to a suitable volumetric flask. Add about 60% of the final volume of Diluent and shake vigorously to disperse the Tablet powder. Sonicate for an additional NLT 60 min with intermediate shaking. Cool to room temperature and dilute with Diluent to volume. Pass a portion through a suitable filter with a 0.45-µm pore size. Discard the first few milliliters of filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 207 nm. For Identification B, use a diode array detector in the range of 200–400 nm.

Column: 4.6-mm × 25-cm; 5-µm packing L7

Temperatures

Autosampler: 15°

Column: 40°

Flow rate: 1.0 mL/min

Injection volume: 10 µL

Run time: NLT 2.1 times the retention time of benzphetamine

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of benzphetamine hydrochloride (C₁₇H₂₁N · HCl) in the portion of Tablets taken:

Result = (r₍ᵤ₎/r₍ₛ₎) × (C₍ₛ₎/C₍ᵤ₎) × 100

r₍ᵤ₎ = peak response of benzphetamine from the Sample solution

r₍ₛ₎ = peak response of benzphetamine from the Standard solution

C₍ₛ₎ = concentration of USP Benzphetamine Hydrochloride RS in the Standard solution (mg/mL)

C₍ᵤ₎ = nominal concentration of benzphetamine hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 93.0%–105.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Use plastic vials for analysis.

Medium: Water; 900 mL

Apparatus 2: 50 rpm

Time: 30 min

Buffer: Dissolve 2.76 g of monobasic sodium phosphate dihydrate in 1000 mL of water. Add 0.5 mL of triethylamine and adjust with phosphoric acid to a pH of 6.0.

Mobile phase: Acetonitrile and Buffer (70:30)

Standard stock solution: 0.55 mg/mL of USP Benzphetamine Hydrochloride RS, prepared as follows. Transfer an adequate amount of USP Benzphetamine Hydrochloride RS to a suitable volumetric flask. Add 5% of the final volume of acetonitrile and sonicate to dissolve. Dilute with Medium to volume.

Standard solution: 0.055 mg/mL of USP Benzphetamine Hydrochloride RS in Medium from Standard stock solution

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 207 nm

Column: 4.6-mm × 25-cm; 5-µm packing L7

Column temperature: 25°

Flow rate: 1.0 mL/min

Injection volume: 10 µL

Run time: NLT 1.8 times the retention time of benzphetamine

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of benzphetamine hydrochloride (C₁₇H₂₁N · HCl) dissolved:

Result = (r₍ᵤ₎/r₍ₛ₎) × C₍ₛ₎ × V × (1/L) × 100

r₍ᵤ₎ = peak response of benzphetamine from the Sample solution

r₍ₛ₎ = peak response of benzphetamine from the Standard solution

C₍ₛ₎ = concentration of USP Benzphetamine Hydrochloride RS in the Standard solution (mg/mL)

V = volume of Medium (mL), 900

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of benzphetamine hydrochloride (C₁₇H₂₁N · HCl) is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Organic Impurities

Solution A: 1.38 g of monobasic sodium phosphate dihydrate in 1000 mL of water

Solution B: Acetonitrile and water (80:20)

Mobile phase: See Table 1.

Diluent: Methanol and water (50:50)

System suitability solution: 0.002 mg/mL each of USP Benzphetamine Hydrochloride RS, USP Benzphetamine Related Compound E RS, and USP Methamphetamine Hydrochloride RS in Diluent. Sonicate to dissolve if necessary.

Sensitivity solution: 0.0001 mg/mL of USP Benzphetamine Hydrochloride RS in Diluent

Standard solution: 0.002 mg/mL of USP Benzphetamine Hydrochloride RS in Diluent. Sonicate to dissolve if necessary.

Sample solution: Nominally 1 mg/mL of benzphetamine hydrochloride in Diluent, prepared as follows. Transfer an adequate amount of benzphetamine hydrochloride from NLT 20 finely powdered Tablets to a suitable volumetric flask. Add about 40% of the final volume of Diluent and shake vigorously to disperse the Tablet powder. Sonicate for an additional NLT 60 min with intermediate shaking. Cool to room temperature and dilute with Diluent to volume. Pass a portion through a suitable filter with a 0.45-µm pore size. Discard the first few milliliters of filtrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 207 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Temperatures

Autosampler: 15°

Column: 40°

Flow rate: 1.2 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution, Sensitivity solution, and Standard solution

Suitability requirements

Resolution: NLT 3.0 between benzphetamine related compound E and benzphetamine, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Tablets taken:

Result = (r₍ᵤ₎/r₍ₛ₎) × (C₍ₛ₎/C₍ᵤ₎) × (1/F) × 100

r₍ᵤ₎ = peak response of each impurity from the Sample solution

r₍ₛ₎ = peak response of benzphetamine from the Standard solution

C₍ₛ₎ = concentration of USP Benzphetamine Hydrochloride RS in the Standard solution (mg/mL)

C₍ᵤ₎ = nominal concentration of benzphetamine hydrochloride in the Sample solution (mg/mL)

F = relative response factor of each individual impurity (see Table 2)

Acceptance criteria: See Table 2.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP Benzphetamine Hydrochloride RS

USP Benzphetamine Related Compound E RS

(1S,2S)-2-[Benzyl(methyl)amino]-1-phenylpropan-1-ol hydrochloride.

C₁₀H₁₅NO · HCl 291.82

USP Methamphetamine Hydrochloride RS

(S)-N-Methyl-1-phenylpropan-2-amine hydrochloride.

C₁₀H₁₅N · HCl 185.69▲ (USP 1-Aug-2019)