Oxazepam

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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C₁₅H₁₁ClN₂O₂ 286.71

2H-1,4-Benzodiazepin-2-one, 7-chloro-1,3-dihydro-3-hydroxy-5-phenyl-, (±)-;

(±)-7-Chloro-1,3-dihydro-3-hydroxy-5-phenyl-2H-1,4-benzodiazepin-2-one CAS RN^®: 604-75-1.

1 DEFINITION

Oxazepam contains NLT 98.0% and NMT 102.0% of oxazepam (C₁₅H₁₁ClN₂O₂), calculated on the dried basis.

2 IDENTIFICATION

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A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K (CN 1-MAY-2020)

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B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. (USP 1-May-2019)

3 ASSAY

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3.1 PROCEDURE

Prepare the System suitability solution, Standard solution, and Sample solution immediately before use.

Solution A: Dissolve 3.5 g of dibasic potassium phosphate in 900 mL of water. Adjust with 1 N sodium hydroxide to a pH of 10.5, and dilute with water to 1 L.

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and water (50:50)

System suitability solution: 1.6 µg/mL each of USP Oxazepam Related Compound A RS and USP Chlordiazepoxide Related Compound A RS, and 0.8 mg/mL of USP Oxazepam RS in Diluent

Standard solution: 0.08 mg/mL of USP Oxazepam RS in Diluent

Sample solution: 0.08 mg/mL of Oxazepam in Diluent

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 235 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection volume: 10 µL

3.3 System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.5 between chlordiazepoxide related compound A and oxazepam related compound A, System suitability solution

Relative standard deviation: NMT 0.73%, Standard solution

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of oxazepam (C₁₅H₁₁ClN₂O₂) in the portion of Oxazepam taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

C_U = concentration of Oxazepam in the Sample solution (mg/mL) (USP 1-May-2019)

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

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.3%

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4.2 ORGANIC IMPURITIES

Prepare the System suitability solution, Standard solution, and Sample solution (USP 1-May-2019) immediately before use.

Solution A, Solution B, Diluent, System suitability solution, and Chromatographic system: Proceed as directed in the Assay.

Mobile phase: See Table 2.

Table 2

Standard solution: 1.6 µg/mL of USP Oxazepam RS in Diluent

Sample solution: 0.8 mg/mL of Oxazepam in Diluent

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

Resolution: NLT 1.5 between chlordiazepoxide related compound A and oxazepam related compound A, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Oxazepam taken:

Result = (r_U/r_S) x (C_S/C_U) x (1/F) x 100

r_U = peak area of any impurity from the Sample solution

r_S = peak area of oxazepam from the Standard solution

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

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

F = relative response factor (see Table 3)

Acceptance criteria: See Table 3. The reporting threshold is 0.05% (USP 1-May-2019)

Table 3

^a 7-Chloro-2-oxo-5-phenyl-2,3-dihydro-1H-benzodiazepin-3-yl acetate.

^b 6-Chloro-4-phenylquinazoline-2-carbaldehyde.

^c 5-Chloro-2-aminobenzophenone.

5 SPECIFIC TESTS

5.1 PH (791)

Sample: A suspension of 1 g of Oxazepam in 50 mL of water

Acceptance criteria: 4.8-7.0

5.2 LOSS ON DRYING (731)

Analysis: Dry at a pressure not exceeding 5 mm of mercury at 105° for 3 h.

Acceptance criteria: NMT 2.0%

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in well-closed containers.

6.2 USP REFERENCE STANDARDS (11)

USP Chlordiazepoxide Related Compound A RS

7-Chloro-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one 4-oxide.

C₁₅H₁₁ClN₂O₂ 286.71

USP Oxazepam RS

USP Oxazepam Related Compound A RS

7-Chloro-5-phenyl-4,5-dihydro-1H-benzodiazepine-2,3-dione.

C₁₅H₁₁ClN₂O₂ 286.71