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 98.0percent and not more than 102.0percent of C13H18ClNO·HCl,calculated on the anhydrous basis.
Packaging and storage— Preserve in well-closed,light-resistant containers.
Identification—
A:Infrared Absorption á197Kñ.
B: The retention time of the major peak in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay.
Water,Method Iá921ñ: not more than 0.5%.
Chromatographic purity—
TEST1—
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 100.0mg per mL.
Standard solutions— Prepare a solution of m-chlorobenzoic acid in methanol containing about 0.5mg 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 0.1mg per mL.
Application volume: 2µL.
Developing solvent system: a mixture of toluene,cyclohexane,and glacial acetic acid (47:47:6).
Procedure— Proceed as directed for Thin-Layer Chromatographyunder Chromatography á621ñ.Locate and quantitate the spots obtained by scanning the entire plate with a suitable densitometer at 254nm.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.
TEST2—
Procedure— Using the chromatograms obtained in the Assay,calculate the percentage of each impurity in the portion of Bupropion Hydrochloride taken by the formula:
100F(ri/rS),
in which Fis the relative response factor for each impurity (see the accompanying table for values);riis the peak response for each impurity obtained from the Assay preparation;and rSis the peak response for bupropion hydrochloride obtained from the Standard preparation.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 1and Test 2being added.
Relative retention time Relative response factor (F) Limit (%)
0.38 0.68 0.5
0.58 0.96 0.2
0.71 2.22 0.1
0.78 0.82 0.1
0.92 0.73 0.2
1.14 — 0.2a
1.63 1.13 0.1
2.30 0.91 0.2
2.74 1.45 0.2
all other peaksb 1.00 0.1
a  The percentage is determined by direct comparison to the area of the peak for bupropion hydrochloride related compound Bobtained from the System suitability solution.
b  Except the peaks with relative retention time of 1.14.
Content of chloride— Dissolve about 50.0mg of Bupropion Hydrochloride,accurately weighed,in 50mLof water,and titrate with 0.1Nsilver nitrate VS,determining the endpoint potentiometrically.Perform a blank determination,and make any necessary corrections.Each mLof 0.1Nsilver nitrate is equivalent to 3.545mg of chloride (Cl):not less than 12.6%and not more than 13.1%of chloride,calculated on the anhydrous basis,is found.
Assay—
Diluent— Prepare a mixture of methanol and water (1:1).
0.025M Phosphate buffer— Dissolve 6.8g of monobasic potassium phosphate in about 1900mLof water.Adjust with 1Nsodium hydroxide to a pHof 7.0,dilute with water to 2000mL,and mix.
Mobile phase— Prepare a filtered and degassed mixture of 0.025M Phosphate buffer,methanol,and tetrahydrofuran (51:39:11).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
System suitability solution— Dissolve accurately weighed quantities of USP Bupropion Hydrochloride Related Compound A RSand USP Bupropion Hydrochloride Related Compound B RSin Diluentto obtain a solution having known concentrations of about 0.025mg of each per mL.
Standard preparation— Transfer 25mg of USP Bupropion Hydrochloride RS,accurately weighed,to a 25-mLvolumetric flask.Dissolve in a portion of Diluent,pipet 2.0mLof the System suitability solutioninto the flask,dilute with Diluentto volume,and mix.
Assay preparation— Transfer about 50mg of Bupropion Hydrochloride,accurately weighed,to a 50-mLvolumetric flask,dissolve in and dilute with Diluentto volume,and mix.
Chromatographic system (see Chromatography á621ñ)— 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 1.1mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative retention times are about 0.92for bupropion hydrochloride related compound Aand 1.14for bupropion hydrochloride related compound B;the resolution,R,between bupropion hydrochloride related compound Aand 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 20µL)of the Standard preparationand the Assay preparationinto 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 Cis the concentration,in mg per mL,of USP Bupropion Hydrochloride RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information— Staff Liaison:Salvador C.Salado,M.S.,Scientist and Latin American Liaison
Expert Committee:(PA3)Pharmaceutical Analysis 3
USP28–NF23Page 296
Pharmacopeial Forum:Volume No.29(4)Page 1011
Phone Number:1-301-816-8165