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Bupropion Hydrochloride
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C13H18ClNO·HCl 276.21
1-Propanone, 1-(3-chlorophenyl)-2-[(1,1-dimethylethyl)amino]-, hydrochloride, (±)-.
(±)-2-(tert-Butylamino)-3¢-chloropropiophenone hydrochloride [31677-93-7].
» Bupropion Hydrochloride contains not less than 98.0 percent and not more than 102.0 percent of C13H18ClNO·HCl, calculated on the anhydrous basis.
Packaging and storage— Preserve in well-closed, light-resistant containers.
Identification—
A: Infrared Absorption 197K.
B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Water, Method I 921: not more than 0.5%.
Change to read:
Related compounds—USP29
TEST 1—
Adsorbent: a 0.25-mm layer of high-performance silica gel, previously washed with methanol.
Test solution— Prepare a solution of Bupropion Hydrochloride in methanol having a concentration of about 100.0 mg per mL.
Standard solutions— Prepare a solution of m-chlorobenzoic acid in methanol containing about 0.5 mg per mL. Dilute this solution quantitatively, and stepwise if necessary, with methanol to obtain solutions having known concentrations of about 0.3, 0.2, and 0.1 mg per mL.
Application volume: 4 µL.USP29
Developing solvent system: a mixture of toluene, cyclohexane, and glacial acetic acid (47:47:6).
Procedure— Proceed as directed for Thin-Layer Chromatography under Chromatography 621. Locate and quantitate the spots obtained by scanning the entire plate with a suitable densitometer at 235 nm.USP29 Plot a standard curve of area versus concentrations of the Standard solutions. From the standard curve, determine the percentages of m-chlorobenzoic acid and any other impurity present: not more than 0.2% of m-chlorobenzoic acid is found; and not more than 0.1% of any other individual impurity is found.
TEST 2—
Diluent, 0.025 M Phosphate buffer, Mobile phase, System suitability solution, and Chromatographic system— Proceed as directed in the Assay.
Standard solution— Use the Standard preparation, prepared as directed in the Assay.
Test solution— Use the Assay preparation.USP29
Procedure— Using the chromatograms obtained in the Assay, calculate the percentage of each impurity in the portion of Bupropion Hydrochloride taken by the formula:
5000(C/W)F(ri / rS)USP29
in which C is the concentration, in mg per mL, of USP Bupropion Hydrochloride RS in the Standard solution; W is the weight, in mg, of sample take to prepare the Test solution;USP29 F is the relative response factor for each impurity (see the accompanying table for values); ri is the peak response for each impurity obtained from the Test solution;USP29 and rS is the peak response for bupropion hydrochloride obtained from the Standard solution.USP29 The limits of impurities are specified in the accompanying table: not more than 0.3% of total unidentified impurities is found; and not more than 1.0% of total impurities is found, the results of Test 1 and Test 2 being added.
Compound Name Relative Retention
Time		 Relative
Response Factor (F)		 Limit (%)
2-(tert-Butylamino)propiophenone hydrochloride about 0.38 0.68 0.5
1-(3-Chlorophenyl)-1,2-
propanedione		 about 0.58 0.96 0.2
2-(tert-Butylamino)-2¢-
chloropropiophenone
hydrochloride		 about 0.71 2.22 0.1
3¢-Chloropropiophenone about 0.78 0.82 0.1
Bupropion hydrochloride
related compound A 		about 0.92 0.73 0.2
Bupropion 1.0 — —
Bupropion hydrochloride
related compound B		 about 1.14 — 0.2*
2-Bromo-3¢-chloropropiophenone about 1.63 1.13 0.1
2-(tert-Butylamino)-3¢,4¢-
chloropropiophenone
hydrochloride		 about 2.30 0.91 0.2
2-(tert-Butylamino)-3¢,5¢-
chloropropiophenone
hydrochloride		 about 2.74 1.45 0.2
Unknown all other peaks 1.00 0.1, individual
*  The percentage is determined by direct comparison to the area of the peak for bupropion hydrochloride related compound B obtained from the System suitability solution.
USP29
Content of chloride— Dissolve about 50.0 mg of Bupropion Hydrochloride, accurately weighed, in 50 mL of water, and titrate with 0.1 N silver nitrate VS, determining the endpoint potentiometrically. Perform a blank determination, and make any necessary corrections. Each mL of 0.1 N silver nitrate is equivalent to 3.545 mg of chloride (Cl): not less than 12.6% and not more than 13.1% of chloride, calculated on the anhydrous basis, is found.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Assay—
Diluent— Prepare a mixture of methanol and water (1:1).
0.025 M Phosphate buffer— Dissolve 6.8 g of monobasic potassium phosphate in about 1900 mL of water. Adjust with 1 N sodium hydroxide to a pH of 7.0, dilute with water to 2000 mL, and mix.
Mobile phase— Prepare a filtered and degassed mixture of 0.025 M Phosphate buffer, methanol, and tetrahydrofuran (51:39:11). Make adjustments if necessary (see System Suitability under Chromatography 621).
System suitability solution— Dissolve accurately weighed quantities of USP Bupropion Hydrochloride Related Compound A RS and USP Bupropion Hydrochloride Related Compound B RS in Diluent to obtain a solution having known concentrations of about 0.025 mg of each per mL.
Standard preparation— Transfer 25 mg of USP Bupropion Hydrochloride RS, accurately weighed, to a 25-mL volumetric flask. Dissolve in a portion of Diluent, pipet 2.0 mL of the System suitability solution into the flask, dilute with Diluent to volume, and mix.
Assay preparation— Transfer about 50 mg of Bupropion Hydrochloride, accurately weighed, to a 50-mL volumetric flask, dissolve in and dilute with Diluent to volume, and mix.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 250-nm detector and a 3.9-mm × 15-cm column that contains 5-µm packing L7. The flow rate is about 1.1 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.92 for bupropion hydrochloride related compound A and 1.14 for bupropion hydrochloride related compound B; the resolution, R, between bupropion hydrochloride related compound A and bupropion hydrochloride is not less than 1.3; and the relative standard deviation for replicate injections is not more than 2.0% determined from bupropion hydrochloride and not more than 5.0% determined from bupropion hydrochloride related compound B.
Procedure— Separately inject equal volumes (about 20 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the quantity, in mg, of C13H18ClNO·HCl in the portion of Bupropion Hydrochloride taken by the formula:
50C(rU / rS)
in which C is the concentration, in mg per mL, of USP Bupropion Hydrochloride RS in the Standard preparation; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information— Staff Liaison : Ravi Ravichandran, Ph.D., Senior Scientist
Expert Committee : (MDPP05) Monograph Development-Psychiatrics and Psychoactives
USP29–NF24 Page 320
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