Bupropion 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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1 DEFINITION

Bupropion Hydrochloride contains NLT 98.0% and NMT 102.0% of bupropion hydrochloride (C₁₃H₁₈ClNO·HCl), calculated on the anhydrous basis.

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

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 〈191〉, Chemical Identification Tests, Chloride

Sample solution: 1 mg/mL of Bupropion Hydrochloride in water (USP 1-Aug-2021)

Acceptance criteria: Meets the requirements of test A

3 ASSAY

Procedure

Diluent: Methanol and water (50:50)

Buffer: 3.4 g/L of monobasic potassium phosphate in water. Adjust with 1 N sodium hydroxide VS (USP 1-Aug-2021) to a pH of 7.0.

Mobile phase: Methanol, tetrahydrofuran, and Buffer (39:11:50)

System suitability solution: 1 mg/mL of USP Bupropion Hydrochloride RS (RB 1-Aug-2021) and 2 µg/mL each of USP Bupropion Related Compound A RS and USP Bupropion Related Compound B RS in Diluent (USP 1-Aug-2021)

Standard solution: 1 mg/mL of USP Bupropion Hydrochloride RS in Diluent (USP 1-Aug-2021)

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

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 250 nm

Column: 3.9-mm × 15-cm; 5-µm packing L7

Flow rate: 1.1 mL/min

Injection volume: 20 µL

Run time: NLT 2 times the retention time of bupropion (USP 1-Aug-2021)

System suitability

Samples: System suitability solution and Standard solution (USP 1-Aug-2021)

[Note—See Table 3 for the relative retention times.]

Suitability requirements

Resolution: NLT 1.3 between bupropion related compound A and bupropion; NLT 1.5 between bupropion and bupropion related compound B, System suitability solution (USP 1-Aug-2021)

Relative standard deviation: NMT 2.0% for bupropion, Standard solution (USP 1-Aug-2021)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of bupropion hydrochloride (C₁₃H₁₈ClNO·HCl) in the portion of Bupropion Hydrochloride taken:

Result = (r₁/r₂) × (C₁/C₂) × 100

r₁ = peak response from the Sample solution

r₂ = peak response from the Standard solution

C₁ = concentration of USP Bupropion Hydrochloride RS in the Standard solution (mg/mL)

C₂ = concentration of Bupropion Hydrochloride in the Sample solution (mg/mL)

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

4 IMPURITIES

Limit of 3-Chlorobenzoic Acid

Protect all analytical solutions from light and use within one day.

Diluent: Methanol and 0.001 N hydrochloric acid TS (USP 1-Aug-2021) (20:80)

Solution A: Acetonitrile and water (10:90). Add 0.4 mL of trifluoroacetic acid per L of the mixture.

Solution B: Acetonitrile and water (95:5). Add 0.3 mL of trifluoroacetic acid per L of the mixture.

Mobile phase: See Table 1.

System suitability stock solution: 0.02 mg/mL of USP Bupropion Related Compound C RS (USP 1-Aug-2021) and 0.012 mg/mL of USP 3-Chlorobenzoic Acid RS in methanol

System suitability solution: 0.002 mg/mL of USP Bupropion Related Compound C RS (USP 1-Aug-2021) and 0.0012 mg/mL of USP 3-Chlorobenzoic Acid RS (USP 1-Aug-2021) from System suitability stock solution in Diluent

Standard stock solution: 0.06 mg/mL of USP 3-Chlorobenzoic Acid RS in methanol

Standard solution: 1.2 µg/mL of USP 3-Chlorobenzoic Acid RS from Standard stock solution in Diluent

Sample solution: 600 µg/mL of Bupropion Hydrochloride in Diluent

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 226 nm

Column: 4.6-mm × 10-cm; 3.5-µm packing L1

Column temperature: 40°

Flow rate: 1.5 mL/min

Injection volume: 5 µL

System suitability

Samples: System suitability solution and Standard solution

[Note—See Table 2 for the relative retention times.]

Suitability requirements

Resolution: NLT 1.5 between bupropion related compound C and 3-chlorobenzoic acid, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of 3-chlorobenzoic acid in the portion of Bupropion Hydrochloride taken:

Result = (r₁/r₂) × (C₁/C₂) × 100

r₁ = peak response of 3-chlorobenzoic acid from the Sample solution

r₂ = peak response of 3-chlorobenzoic acid from the Standard solution

C₁ = concentration of USP 3-Chlorobenzoic Acid RS in the Standard solution (µg/mL)

C₂ = concentration of Bupropion Hydrochloride in the Sample solution (µg/mL)

Acceptance criteria: See Table 2.

a Included for system suitability purposes only. This impurity is quantified using the test for Organic Impurities. (USP 1-Aug-2021)

Organic Impurities

Diluent, Buffer, Mobile phase, System suitability solution (USP 1-Aug-2021) Standard solution, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

Sensitivity solution: 0.0005 mg/mL of USP Bupropion Hydrochloride RS in Diluent

Mode: LC

Detector: UV 250 nm

Column: 3.9-mm × 15-cm; 5-µm packing L7

Flow rate: 1.1 mL/min

Injection volume: 20 µL

Run time: NLT 3 times the retention time of bupropion (USP 1-Aug-2021)

System suitability

Samples: System suitability solution and Sensitivity solution (USP 1-Aug-2021)

[Note—See Table 3 for the relative retention times.]

Suitability requirements

Resolution: NLT 1.3 between bupropion related compound A and bupropion; NLT 1.5 between bupropion and bupropion related compound B, System suitability solution (USP 1-Aug-2021)

Relative standard deviation: NMT 2.0% for bupropion; NMT 5.0% for bupropion related compound B, System suitability solution

Signal-to-noise ratio: NLT 10, Sensitivity solution (USP 1-Aug-2021)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Bupropion Hydrochloride taken:

Result = (r₁/r₂) × (C₁/C₂) × (1/F) × 100

r₁ = peak response for each impurity from the Sample solution

r₂ = peak response for bupropion from the Standard solution

C₁ = concentration of USP Bupropion Hydrochloride RS in the Standard solution (mg/mL)

C₂ = concentration of Bupropion Hydrochloride in the Sample solution (mg/mL)

F = relative response factor for each impurity relative to bupropion (see Table 3)

Acceptance criteria: See Table 3. The reporting threshold is 0.05%. (USP 1-Aug-2021)

a 2-(tert-Butylamino)-1-phenylpropan-1-one; also known as 2-(tert-butylamino)propiophenone.

b 1-(3-Chlorophenyl)propane-1,2-dione; also known as 1-(3-chlorophenyl)-1,2-propanedione.

c 2-(tert-Butylamino)-1-(2-chlorophenyl)propan-1-one; also known as 2-(tert-butylamino)-2′-chloropropiophenone.

d 1-(3-Chlorophenyl)propan-1-one; also known as 3′-chloropropiophenone.

e 2-(tert-Butylamino)-1-(3,4-dichlorophenyl)propan-1-one; also known as 2-(tert-butylamino)-3′,4′-dichloropropiophenone.

f 2-(tert-Butylamino)-1-(3,5-dichlorophenyl)propan-1-one; also known as 2-(tert-butylamino)-3′,5′-dichloropropiophenone.

g Sum of all impurities found in the tests for Limit of 3-Chlorobenzoic Acid and Organic Impurities.

5 SPECIFIC TESTS

Water Determination 〈921〉, Method I: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed, light-resistant containers. Store at room temperature.

USP Reference Standards 〈11〉

USP Bupropion Hydrochloride RS

USP Bupropion Related Compound A RS

[Note—May also be labeled as USP Bupropion Hydrochloride Related Compound A RS.]

2-(tert-Butylamino)-1-(4-chlorophenyl)propan-1-one hydrochloride;

Also known as (USP 1-Aug-2021) 2-(tert-Butylamino)-4′-chloropropiophenone hydrochloride.

C₁₃H₁₈ClNO·HCl 276.21

USP Bupropion Related Compound B RS

[Note—May also be labeled as USP Bupropion Hydrochloride Related Compound B RS.]

2-(tert-Butylamino)-1-(3-bromophenyl)propan-1-one hydrochloride;

Also known as (USP 1-Aug-2021) 2-(tert-Butylamino)-3′-bromopropiophenone hydrochloride.

C₁₃H₁₈BrNO·HCl 320.66

USP Bupropion Related Compound C RS

[Note—May also be labeled as USP Bupropion Hydrochloride Related Compound C RS] (USP 1-Aug-2021)

1-(3-Chlorophenyl)-2-hydroxypropan-1-one.

C₉H₉ClO₂ 184.62

USP 3-Chlorobenzoic Acid RS

3-Chlorobenzoic acid.

C₇H₅ClO₂ 156.57