Amoxapine

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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C₁₇H₁₆ClN₃O 313.78

Dibenz[b,f][1,4]oxazepine, 2-chloro-11-(1-piperazinyl)-;

2-Chloro-11-(1-piperazinyl)dibenz[b,f][1,4]oxazepine CAS RN®: 14028-44-5; UNII: R63VQ857OT.

1 DEFINITION

Amoxapine contains NLT 98.0% and NMT 102.0% of amoxapine (C₁₇H₁₆ClN₃O), calculated on the dried basis. 

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Buffer: 3.9 g/L of ammonium acetate in water adjusted with acetic acid or diluted ammonia solution to a pH of 7.3 Mobile phase: Acetonitrile and Buffer (30:70)

Diluent: Acetonitrile and Buffer (70:30)

System suitability solution: 0.1 mg/mL each of USP Amoxapine RS and USP Amoxapine Related Compound G RS in Diluent Standard solution: 0.1 mg/mL of USP Amoxapine RS in Diluent

Sample solution: 0.1 mg/mL of Amoxapine in Diluent

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 7.5-cm; 2.5-µm or 2.7-µm packing L1

Column temperature: 35°

Flow rate: 1.2 mL/min

Injection volume: 10 µL

3.2 System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for amoxapine and amoxapine related compound G are 1.0 and 1.3, respectively.] Suitability requirements

Resolution: NLT 1.5 between amoxapine and amoxapine related compound G, System suitability solution Tailing factor: 0.8–1.8, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of amoxapine (C₁₇H₁₆ClN₃O) in the portion of Amoxapine taken:

Result = (r_U /r_S) × (C_S /C_U) × 100

r_U = peak response of amoxapine from the Sample solution

r_S = peak response of amoxapine from the Standard solution

C_S = concentration of USP Amoxapine RS in the Standard solution (mg/mL)

C_U = concentration of Amoxapine in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0% on the dried basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Solution A: 3.9 g/L of ammonium acetate in water adjusted with acetic acid or diluted ammonia solution to a pH of 7.3 Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Solution A and Solution B (30:70)

System suitability solution: 1 mg/mL of USP Amoxapine RS and 1.5 µg/mL of USP Amoxapine Related Compound G RS in Diluent Standard solution: 1 µg/mL of USP Amoxapine RS, and 1.5 µg/mL each of USP Amoxapine Related Compound G RS and USP Amoxapine Related Compound D RS in Diluent

Sample solution: 1000 µg/mL of Amoxapine in Diluent

Chromatographic system: Proceed as directed in the Assay.

System suitability

Samples: System suitability solution and Standard solution

[Note—See Table 2 for the relative retention times.]

Suitability requirements

Peak-to-valley ratio: NLT 3 between amoxapine and amoxapine related compound G, System suitability solution

Relative standard deviation: NMT 5.0% each for amoxapine, amoxapine related compound G, and amoxapine related compound D, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of amoxapine related compound G and amoxapine related compound D in the portion of Amoxapine taken:

Result = (r_U /r_S) × (C_S /C_U) × 100

r_U = peak response of amoxapine related compound G or amoxapine related compound D from the Sample solution

r_S = peak response of amoxapine related compound G or amoxapine related compound D from the Standard solution

C_S = concentration of USP Amoxapine Related Compound G RS or USP Amoxapine Related Compound D RS in the Standard solution (µg/mL)

C_U = concentration of Amoxapine in the Sample solution (µg/mL)

Calculate the percentage of any other impurity in the portion of Amoxapine taken:

Result = (r_U /r_S) × (C_S /C_U) × 100

r_U= peak response of any other impurity from the Sample solution

r_S = peak response of amoxapine from the Standard solution

C_S = concentration of USP Amoxapine RS in the Standard solution (µg/mL)

C_U= concentration of Amoxapine in the Sample solution (µg/mL)

Acceptance criteria: See Table 2. Disregard peaks that are less than 0.02% of the amoxapine peak.

Table 2

^a N-[2-(4-Chlorophenoxy)phenyl]piperazine-1-carboxamide.

^b 2-(4-Chlorophenoxy)aniline.

^c Ethyl [2-(4-Chlorophenoxy)phenyl]carbamate.

^d 4-(2-Chlorodibenzo[b,f][1,4]oxazepin-11-yl)-N-[2-(4-chlorophenoxy)phenyl]piperazine-1-carboxamide.

^e 1,4-Bis(2-chlorodibenzo[b,f][1,4]oxazepine-11-yl)piperazine.

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry at 105° for 4 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers.

USP Reference Standards 〈11〉

USP Amoxapine RS

USP Amoxapine Related Compound D RS

2-Chlorodibenzo[b,f]-[1,4]-oxazepin-11-one.

C₁₃H₈ClNO₂ 245.66

USP Amoxapine Related Compound G RS

3-Chloro-11-(piperazin-1-yl)dibenzo[b,f][1,4]oxazepine.

C₁₇H₁₆ClN₃ O 313.78