Bupropion Hydrochloride
(bue proe' pee on hye'' droe klor' ide).
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C13H18ClNO·HCl 276.20
1-Propanone, 1-(3-chlorophenyl)-2-[(1,1-dimethylethyl)amino]-, hydrochloride, (±)-;    
(±)-2-(tert-Butylamino)-3¢-chloropropiophenone hydrochloride     [31677-93-7].
DEFINITION
Bupropion Hydrochloride contains NLT 98.0% and NMT 102.0% of C13H18ClNO·HCl, calculated on the anhydrous basis.
IDENTIFICATION
•  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, Chloride 191: Meets the requirements for the silver nitrate precipate test
Sample solution:  1 mg/mL of Bupropion Hydrochloride
ASSAY
•  Procedure
Diluent:  Methanol and water (1:1)
Buffer:  3.4 g/L of monobasic potassium phosphate in water. Adjust with 1 N sodium hydroxide to a pH of 7.0.
Mobile phase:  Methanol, tetrahydrofuran, and Buffer (39:11:51)
Standard solution:  1 mg/mL of USP Bupropion Hydrochloride RS and 2 µg/mL each of USP Bupropion Hydrochloride Related Compound A RS and USP Bupropion Hydrochloride Related Compound B RS in Diluent
Sample solution:  1 mg/mL of Bupropion Hydrochloride in Diluent
Chromatographic system 
Mode:  LC
Detector:  UV 250 nm
Column:  3.9-mm × 15-cm; 5-µm packing L7
Flow rate:  1.1 mL/min
Injection size:  20 µL
System suitability 
Sample:  Standard solution
[Note—The relative retention times for bupropion hydrochloride related compound A, bupropion hydrochloride, and bupropion hydrochloride related compound B are about 0.92, 1.0, and 1.14, respectively. ]
Suitability requirements 
Resolution:  NLT 1.3 between bupropion hydrochloride related compound A and bupropion hydrochloride
Relative standard deviation:  NMT 2.0% determined from bupropion hydrochloride; NMT 5.0% determined from bupropion hydrochloride related compound B
Analysis:  Calculate the percentage of C13H18ClNO·HCl in the portion of Bupropion Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response from the Sample solution
rS== peak response from the Standard solution
CS== concentration of USP Bupropion Hydrochloride RS in the Standard solution (mg/mL)
CU== concentration of Bupropion Hydrochloride in the Sample solution (mg/mL)
Acceptance criteria:  98.0%–102.0% on the anhydrous basis
IMPURITIES
Organic Impurities 
•  Procedure 1: Limit of m-Chlorobenzoic Acid
Mobile phase:  Acetonitrile, trifluoroacetic acid, and water (35:0.1:65)
System suitability solution:  1.0 mg/mL of USP Bupropion Hydrochloride RS and 4 µg/mL of m-chlorobenzoic acid in Mobile phase
Sample solution:  2 mg/mL of Bupropion Hydrochloride in Mobile phase
Chromatographic system 
Mode:  LC
Detector:  UV 235 nm
Column:  4.6-mm × 25-cm; 5-µm packing L1
Flow rate:  1 mL/min
Injection size:  20 µL
Run time:  2.7 times the retention time of m-chlorobenzoic acid
System suitability 
Sample:  System suitability solution
[Note—The relative retention times for bupropion hydrochloride and m-chlorobenzoic acid are 1.0 and 2.0, respectively. ]
Suitability requirements 
Resolution:  NLT 10.0 between the bupropion and m-chlorobenzoic acid peaks
Relative standard deviation:  NMT 5.0% for the m-chlorobenzoic acid peak
Analysis 
Sample:  Sample solution
Calculate the percentage of m-chlorobenzoic acid in the portion of Bupropion Hydrochloride taken:
Result = (rU/rT) × 100
rU== peak response of m-chlorobenzoic acid from the Sample solution
rT== sum of the responses of all the peaks from the Sample solution
Acceptance criteria 
m-chlorobenzoic acid:  NMT 0.2%
•  Procedure 2
Diluent, Buffer, Mobile phase, Standard solution, Sample solution, Chromatographic system, and System suitability:  Proceed as directed in the Assay.
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Bupropion Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
rU== peak response for each impurity from the Sample solution
rS== peak response for bupropion hydrochloride from the Standard solution
CS== concentration of USP Bupropion Hydrochloride RS in the Standard solution (mg/mL)
CU== concentration of Bupropion Hydrochloride in the Sample solution (mg/mL)
F== relative response factor for each impurity relative to bupropion
Calculate the percentage of bupropion hydrochloride related compound B in the portion of Bupropion Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response of bupropion hydrochloride related compound B from the Sample solution
rS== peak response of bupropion hydrochloride related compound B from the Standard solution
CS== concentration of USP Bupropion Hydrochloride Related Compound B RS in the Standard solution (mg/mL)
CU== concentration of Bupropion Hydrochloride in the Sample solution (mg/mL)
Acceptance criteria 
Individual impurities:  See Impurity Table 1.
Total impurities:  The limits of impurities are specified in the accompanying table: NMT 0.3% of total unidentified impurities is found; and NMT 1.0% of total impurities is found, the results of Procedure 1 and Procedure 2 being added.
Impurity Table 1
Name Relative
Retention
Time
Relative
Response
Factor
Acceptance
Criteria,
NMT (%)
2-(tert-Butylamino)propiophenone hydrochloride 0.38 1.5 0.5
1-(3-Chlorophenyl)-1,2-propanedione 0.58 1.0 0.2
2-(tert-Butylamino)-2¢-chloropropiophenone hydrochloride 0.71 0.45 0.1
3¢-Chloropropiophenone 0.78 1.2 0.1
Bupropion hydrochloride related compound A 0.92 1.4 0.2
Bupropion 1.0
Bupropion hydrochloride related compound B 1.14 0.2
2-Bromo-3¢-chloropropiophenone 1.63 0.88 0.1
2-(tert-Butylamino)-3¢,4¢-chloropropiophenone hydrochloride 2.30 1.1 0.2
2-(tert-Butylamino)-3¢,5¢-chloropropiophenone hydrochloride 2.74 0.69 0.2
Any individual impurity 1.0 0.1
SPECIFIC TESTS
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in well-closed, light-resistant containers.
•  USP Reference Standards 11
USP Bupropion Hydrochloride RS Click to View Structure
USP Bupropion Hydrochloride Related Compound A RS Click to View Structure
2-(tert-Butylamino)-4¢-chloropropiophenone hydrochloride.
    C13H18ClNO·HCl        276.20
USP Bupropion Hydrochloride Related Compound B RS Click to View Structure
2-(tert-Butylamino)-3¢-bromopropiophenone hydrochloride.
    C13H18BrNO·HCl        320.66
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Principal Scientific Liaison
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USP35–NF30 Page 2403
Pharmacopeial Forum: Volume No. 36(2) Page 383