भारतीय भेषज संहिता आयोग
Bupropion Hydrochloride
C13H18ClNO,HCl Mol. Wt. 276.2
Bupropion Hydrochloride is 1-propanone,1-(3-chlorophenyl)-2-[(1,1-dimethylethyl)amino]-, hydrochloride, (±) -;(±) -2- (tert-butylamino)-3ʹ-chloropropiophenone hydrochloride.
Bupropion Hydrochloride contains not less than 98.0 per cent and not more than 102.0 per cent of C13H18ClNO,HCl, calculated on the anhydrous basis.
Category.Antidepressant.
Dose.Orally, 100 mg twice daily.
Description.A white powder.
Identification
- Determine by infrared absorption spectrophotometry (2.4.6). Compare the spectrum with that obtained frombupropion hydrochloride RSor with the reference spectrum of bupropion hydrochloride.
B.In the Assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution.
- Gives the reaction (A) of chlorides (2.3.1).
Tests
Related substances.Determine by liquid chromatography (2.4.14).
Use the test solution, reference solution and chromatographic system as described under Assay.
Name Relative Correction
retention time factor
Deschlorobupropion1 0.38 0.66
Bupropiondionederivative2 0.58 1.0
O-Bupropion3 0.71 2.22
Chloropropiophenone4 0.78 0.83
Bupropionhydrochloriderelated compound A 0.92 0.71
Bupropion 1.0 ---
Bupropionhydrochloriderelated compound B 1.14 1.23
Bromochloropropionphenone5 1.63 1.13
4-Chlorobupropion6 2.30 0.90
5-Chlorobupropion7 2.74 1.44
UnknownImpurity --- 1.0
12-(tert-butylamino)-1-phenylpropan-1-one ; 2-( tert-butylamino) propiophenone,
21-(3-chlorophenyl) propane-1,2-dione ; 1-(3-chlorophenyl) -1,2-propanedione,
32-( tert-butylamino)-1-(2-chlorophenyl) propan-1-one ; 2-(tert-butylamino)-2’-chloropropiophenone,
4 1-( 3- chlorophenyl) propan-1-one ; 3’-chloropropiophenone,
52-Bromo-1-(3-chlorophenyl) propan-1-one ; 2-bromo-3’-chloropropiophenone,
62-(tert-butylamino)1-(3,4-dichlorophenyl) propan-1-one ; 2-(tert-butylamino-3’,4’-dichloropropiophenone,
72-(tert-butylamino)-1-(3,5-dichlorophenyl) propan-1-one ; 2-(tert-butylamino)-3’,5’-dichloropropiophenone.
Inject the reference solution.The test is not valid unless the resolution between bupropion hydrochloride related compound A, bupropion hydrochloride related compound B and bupropion is not less than 1.3 and the relative standard deviation for bupropion is not more than 2.0 per cent and bupropion hydrochloride related compound B is not more than 5.0 per cent.
Inject the reference solution and the test solution. In the chromatogram obtained with the test solution, the area of deschloro bupropion peak is not more than 0.005 times the area of the principal peak in the chromatogram obtained with reference solution (0.5 per cent). In the chromatogram obtained with the test solution, the area of bupropion dione derivative, bupropion hydrochloride related compound A, bupropion hydrochloride related compound B, 4-chlorobupropion and 5- chlorobupropion peak is not more than 0.002 times the area of the principal peak in the chromatogram obtained with reference solution (0.2 per cent). In the chromatogram obtained with the test solution, the area of o-bupropion, chloropropiophenone, bromochloropropionphenone and any other single impurity peak is not more than 0.001 times the area of the principal peak in the chromatogram obtained with reference solution (0.1 per cent). The sum of the areas of all the peaks (3-chlorobenzoic acid and organic impurities) other than the principal peak, is not more than 0.01 times the area of the principal peak in the chromatogram obtained with reference solution (1.0 per cent).
Limit of 3-Chlorobenzoic Acid. Determine by liquid chromatography (2.4.14).
Solvent mixture.20 volumes of methanol and 80 volumes of0.001M hydrochloric acid.
NOTE —Prepare the solutions immediately before use and protect from light.
Test solution. Dissolve 60 mg of the substance under examination in 100.0 ml of the solvent mixture.
Reference solution(a). A 0.002 per cent w/v solution of bupropion hydrochloride related compound C RS (1-(3-chlorophenyl)-2-hydroxypropan-1-one),bupropion hydrochloride related compound F RS((1-(3-chlorophenyl)-1-hydroxypropan-2-one) and 0.0012 per cent w/v solution of 3-chlorobenzoic acid RS in methanol.
Reference solution(b). Dilute 10.0 ml of the reference solution (a) to 100.0 ml with the solvent mixture.
Reference solution(c). A 0.012 per cent w/v solution of of 3-chlorobenzoic acid RS in methanol. Dilute 1.0 ml of this solution to 100.0 ml with the solvent mixture.
Chromatographic system
– a stainless steel column 10 cm x 4.6 mm, packed with octadecylsilane bonded to porous silica (3.5 µm),
– column temperature. 40º,
– mobile phase: A. a mixture of 10 volumes of acetonitrile and 90 volumes of water add 0.4 ml oftrifluoroacetic acid,
- a mixture of 95 volumes of acetonitrile and 5 volumes of water add 0.3 ml oftrifluoroacetic acid,
– a gradient programme using the conditions given below,
– flow rate: 1.5 ml per minute,
– spectrophotometer set at 226 nm,
– injection volume: 5 µl.
Time Mobile phase A Mobile phase B
(in min.) (per cent v/v) (per cent v/v)
0 90 10
3.4 87 13
10.0 15 85
10.1 0 100
13.0 0 100
13.2 90 10
19.0 90 10
Name Relative
retention time
Bupropion hydrochloride 1.0
Bupropionhydrochloride related compound F 1.71
Bupropionhydrochloride related compound C 1.75
3- Chlorobenzoic acid 1.80
Inject reference solution (b).The test is not valid unless the resolution between bupropion hydrochloride related compound F,bupropion hydrochloride related compound C and 3-chlorobenzoic acid is not less than 1.5 and , the relative standard deviation for replicate injections is not more than 5.0 per cent.
Inject reference solution (c) and the test solution. In the chromatogram obtained with the test solution, the area of 3-chlorobenzoic acid peak is not more than the area of the principal peak in the chromatogram obtained with reference solution (c) (0.2 per cent).
Water (2.3.43). Not more than 0.5 per cent.
Assay. Determine by liquid chromatography (2.4.14).
Solvent mixture.50 volumes of methanol and 50 volumes of water.
Test solution. Dissolve 100 mg of the substance under examination in 100.0 ml of the solvent mixture.
Reference solution. A 0.1 per cent w/v solution ofbupropion hydrochloride RS and 0.0002 per cent w/v solution each of bupropion hydrochloride related compound A RS (2-tert-butylamino)-4’-chloropropiophenone hydrochloride) and bupropion hydrochloride related compound B RS(2-tert-butylamino)3’bromopropiophenone hydrochloride) in solvent mixture.
Chromatographic system
– a stainless steel column 15 cm x 3.9 mm, packed with octylsilane bonded to porous silica (5 µm),
– mobile phase: a mixture of 50 volumes of a buffer solution prepared by dissolving 3.4 g of monobasic potassium phosphate in 1000 ml of water, adjusting the pH to 7.0 with 1M sodium hydroxide solution, and diluting to 1000 ml with water, 11 volumes of tetrahydrofuran and 39 volumes of methanol,
– flow rate: 1.1 ml per minute,
– spectrophotometer set at 250 nm,
– injection volume: 20 µl.
Inject the reference solution.The test is not valid unless the resolution between bupropion hydrochloride related compound A, bupropion hydrochloride related compound B and bupropion is not less than 1.3 and , the relative standard deviation for replicate injections is not more than 2.0 per cent.
Inject the reference solution and the test solution.
Calculate the content of C13H18ClNO,HCl.
Storage. Store protected from light and moisture, at temperature not exceeding 30º.
Solubility.Soluble in Water,0.1M hydrochloric acid and inethanol (95 per cent).
