Amoxapine
C17H16ClN3O Mol. Wt. 313.8
Amoxapine is Dibenz[b,f][1,4] oxazepine, 2-chloro-11-(1-piperazinyl)-;2-chloro-11-(1-piperazinyl) dibenz[b,f] [1,4] oxazepine.
Amoxapine contains not less than 98.0 per cent and not more than 102.0 per cent of C17H16ClN3O, calculated on the dried basis.
Category. Antidepressant.
Dose. Orally, 50 mg twice or three times daily.
Description. A white to yellowish crystalline powder.
Identification
- Determine by infrared absorption spectrophotometry (2.4.6). Compare the spectrum with that obtained fromamoxapine RSor with the reference spectrum of amoxapine.
- 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 (b).
Tests
Related substances. Determine by liquid chromatography (2.4.14).
Buffer Solution. Dissolve 3.9 g of ammonium acetate in 1000 ml of water, adjust the pH 7.3 with acetic acid or dilute ammonia.
Solvent mixture. 30 volumes of buffer solution and 70 volumes of acetonitrile.
Test solution. Dissolve 100 mg of the substance under examination in 100.0 ml of the solvent mixture.
Reference solution(a). A 0.1 per cent w/v solution of amoxapine RS and 0.00015 per cent w/v solution of amoxa-pine related compound G RS [ 3-chloro-11-(piperazin-1-yl) dibenzo[b,f][1,4] oxazepine]in solvent mixture.
Reference solution(b). A 0.0001 per cent w/v solution of amoxapine RS and 0.00015 per cent w/v each solution of amoxapine related compound G RS [3-chloro-11-(piperazin-1-yl) dibenzo[b,f][1,4] oxazepine] and amoxapine related compound D RS [2-chlorodibenzo[b,f]-[1,4]-oxazepin-11-one] in solvent mixture.
Use the chromatographic system as described under Assay except gradient programme.
Time Mobile phase A Mobile phase B
(in min.) (per cent v/v) (per cent v/v)
0 70 30
5 70 30
7.5 60 40
15 60 40
20 20 80
25 20 80
30 70 30
35 70 30
Name Relative
retention time
Chlorophenoxyanilineurea analog1 0.57
Amoxapine 1.0
Amoxapine related compound G 1.4
Amoxapine related compound D 1.7
Chlorophenoxyaniline2 2.9
Chlorophenoxyaniline carbamate3 3.8
N-Carbamoyl amoxapine4 4.3
Amoxapine dimer5 5.0
1N-[2-(4-Chlorophenoxy) phenyl] piperazine-1-carboxamide,
22-(4-Chlorophenoxy) aniline,
3Ethyl[2-(4-Chlorophenoxy) phenyl] carbamate,
4 4-(2-Chlorodibenzo[b,f] [1,4] oxazepin-11-yl)-N-[2-(4-chlorophenoxy) phenyl] piperazine-1-carboxamide,
51,4-Bis( 2-chlorodibenzo[b,f] [1,4] oxazepine-11-yl) piperazine.
Inject reference solutions (a). In the chromatogram obtained with reference solution (a) the peak to valley ratio between the peaks due to amoxapine and amoxapine related compound G is not less than 3.
Inject the reference solution (b). The test is not valid unless the relative standard deviation each for amoxapine, amoxapine related compound G and amoxapine related compound D peaks is not more than 5.0 per cent.
Inject reference solution (b) and the test solution. In the chromatogram obtained with the test solution, the area of peaks due to chlorophenoxyaniline urea analog, chlorophenoxyaniline, chlorophenoxyanilinecarbamate, N-carbamoylamoxapine, amoxapine dimer and any unknown impurity peak is not more than 0.66 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.1 per cent). In the chromatogram obtained with the test solution, the area of amoxapine related compound G and amoxapine related compound D peak is not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (0.15 per cent).The sum of the areas of all the peaks other than the principal peak, is not more than 3.3 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.5 per cent).Ignore any peak with an area less than 0.13 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.02 per cent).
Loss on drying (2.4.19). Not more than 0.5 per cent, determined on 1.0 g by drying in an oven at 105° for 4 hours.
Sulphated ash (2.3.18). Not more than 0.1 per cent.
Assay. Determine by liquid chromatography (2.4.14).
Solvent mixture.70 volumes of acetonitrile and 30 volumes of buffer solution.
Test solution. Dissolve 10 mg of the substance under examination in 50 ml of solvent mixture and dilute to 100.0 ml of the solvent mixture.
Reference solution (a). A 0.01 per cent w/v solution of amoxapine RS and amoxapine related compound G RS [ 3-chloro-11-( piperazin-1-yl) dibenzo[ b,f] [1,4] oxazepine]in solvent mixture.
Reference solution (b).A 0.01 per cent w/v solution of amoxapine RS in solvent mixture.
Chromatographic system
– a stainless steel column 7.5 cm x 4.6 mm, packed with octadecylsilane bonded to porous silica (2.7 µm),
– column temperature: 35º,
– mobile phase: a mixture of 70 volumes of a buffer solution prepared by dissolving 3.9 g of ammonium acetate in 1000 ml of water, adjusting the pH to 7.3 with acetic acid or dilute ammonia solution, and 30 volumes of acetonitrile,
– flow rate: 1.2 ml per minute,
– spectrophotometer set at 254 nm,
– injection volume: 10 µl.
Name Relative
retention time
Amoxapine 1.0
Amoxapine related compound G 1.3
Inject reference solution (a).The test is not valid unless the resolution between amoxapine related compound G, and amoxapine is not less than 1.5.
Inject reference solution (b). The tailing factor is between 0.8 to 1.8 and the relative standard deviation for replicate injections is not more than 0.73 per cent.
Inject reference solution (b) and the test solution.
Calculate the content of C17H16ClN3O.
Storage. Store in tightly closed containers.