Benzphetamine Hydrochloride

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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(+)-N-Benzyl-N, α-dimethylphenethylamine hydrochloride;

(S)-N-Benzyl-N-methyl-1-phenylpropan-2-amine hydrochloride CAS RN: 5411-22-3; UNII: 43DWT87QT7

1 DEFINITION

Benzphetamine Hydrochloride contains NLT 98.0% and NMT 102.0% of benzphetamine hydrochloride (C₁₇H₂₁N· HCl), calculated on the dried basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197A or 197K (CN 1-May-2020)

B. The retention time of the benzphetamine peak of the Sample solution corresponds to that of the System suitability solution, as obtained in the Enantiomeric Purity test.

C. IDENTIFICATION TESTS-GENERAL (191), Chemical Identification Tests. Chloride: Meets the requirements

3 ASSAY

PROCEDURE

Buffer: 0.01 M monobasic sodium phosphate in water

Solution A: Acetonitrile and Buffer (10:90)

Solution B: Acetonitrile and water (70:30)

Mobile phase: See Table 1.

Table 1

Diluent: Methanol and water (50:50)

Standard solution: 0.1 mg/mL of USP Benzphetamine Hydrochloride RS in Diluent

Sample solution: 0.1 mg/mL of Benzphetamine Hydrochloride in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 207 nm

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

Column temperature: 30°

Flow rate: 1.0 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.5

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of benzphetamine hydrochloride (C₁₇H₂₁N· HCl) in the portion of Benzphetamine Hydrochloride 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 = concentration of Benzphetamine Hydrochloride in the Sample solution (mg/mL)

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

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.2%

4.1 Organic Impurities

Buffer, Solution A, Solution B, and Diluent: Prepare as directed in the Assay.

Mobile phase: See Table 2

Table 2

System suitability solution: 1 mg/mL of USP Benzphetamine Hydrochloride RS and 0.001 mg/mL each of USP Benzphetamine Related Compound E RS and USP Benzphetamine Related Compound F RS in Diluent

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

Standard solution: 0.001 mg/mL of USP Benzphetamine Hydrochloride RS in Diluent

Sample solution: 1 mg/mL of Benzphetamine Hydrochloride in Diluent

Chromatographic system: Proceed as directed in the Assay, except for Injection volume.

Injection volume: 20 µL

System suitability

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

Suitability requirements

Resolution: NLT 2.0 between benzphetamine related compound E and benzphetamine; NLT 2.0 between benzphetamine related compound F 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 Benzphetamine Hydrochloride 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 = concentration of Benzphetamine Hydrochloride in the Sample solution (mg/mL)

F = relative response factor of each individual impurity (see Table 3)

Acceptance criteria: See Table 3.

Table 3

^a Benzphetamine related compound A monitored in the Enantiomeric Purity test is not included in the total impurities.

4.2 Limit of Benzyl Chloride

Buffer: 0.01 M monobasic potassium phosphate in water. Adjust with phosphoric acid to a pH of 3.0.

Mobile phase: Acetonitrile and Buffer (50:50)

Diluent: Acetonitrile and water (50:50)

Standard solution: 0.001 mg/mL of USP Benzyl Chloride RS in Diluent

Sample solution: 10 mg/mL of Benzphetamine Hydrochloride in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 207 nm

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

Column temperature: 30°

Flow rate: 1.0 mL/min

Injection volume: 20 µL

Run time: NLT 1.4 times the retention time of benzyl chloride

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 5.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of benzyl chloride in the portion of Benzphetamine Hydrochloride taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of benzyl chloride from the Sample solution

r_s = peak response of benzyl chloride from the Standard solution

C_s = concentration of USP Benzyl Chloride RS in the Standard solution (mg/mL)

C_u = concentration of Benzphetamine Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: NMT 0.010%

4.3 Enantiomeric Purity

Mobile phase: Methanol and diethylamine (100: 0.1)

System suitability solution: 0.1 mg/mL each of USP Benzphetamine Hydrochloride RS and USP Benzphetamine Related Compound A RS in

Mobile phase

Standard solution: 0.0015 mg/mL of USP Benzphetamine Related Compound A RS in Mobile phase

Sample solution: 1 mg/mL of Benzphetamine Hydrochloride in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 207 nm

Column: 4.6-mm x 25-cm; 5-µm packing 180

Flow rate: 0.8 mL/min

Injection volume: 35 µL

Run time: NLT 1.9 times the retention time of benzphetamine

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.5 between benzphetamine and benzphetamine related compound A, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of benzphetamine related compound A in the portion of Benzphetamine Hydrochloride taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of benzphetamine related compound A from the Sample solution

r_s = peak response of benzphetamine related compound A from the Standard solution

C_s = concentration of USP Benzphetamine Related Compound A RS in the Standard solution (mg/mL)

C_u = concentration of Benzphetamine Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: See Table 4.

Table 4

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry at 105° for 3h.

Acceptance criteria: NMT 1.0%

pH 〈791〉

Sample solution: 20 mg/mL of Benzphetamine Hydrochloride in water

Acceptance criteria: 4.0–6.0

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 A RS

(R)-N-Benzyl-N-methyl-1-phenylpropan-2-amine hydrochloride.

C₁₇H₂₁N · HCl            275.82

USP Benzphetamine Related Compound E RS

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

C₁₇H₂₁NO · HCl         291.82

USP Benzphetamine Related Compound F RS

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

C₁₇H₂₁NO · HCl         297.87

USP Benzyl Chloride RS

(Chloromethyl)benzene.

C₇H₇Cl                        126.58 _{(USP 1-Aug-2019)}