Alprazolam

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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C₁₇H₁₃CIN₄ 308.76

4H-[1,2,4] Triazolo [4,3-a] [1,4]benzodiazepine, 8-chloro-1-methyl-6-phenyl-;

8-Chloro-1-methyl-6-phenyl-4H-s-triazolo [4,3-a][1,4] benzodiazepine CAS RN®: 28981-97-7; UNII: YU55MQ3IZY.

1 DEFINITION

Alprazolam contains NLT 98.0% and NMT 102.0% of C₁₇H₁₃CIN₄

[CAUTION-Care should be taken to prevent inhaling particles of Alprazolam and exposing the skin to it.]

2 IDENTIFICATION

Change to read:

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

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

3 ASSAY

3.1 PROCEDURE

Diluent: Acetonitrile and water (1:1)

Buffer: 1.4 g/L of monobasic potassium phosphate in water

Mobile phase: Acetonitrile and Buffer (1:1)

Standard solution: 25 µg/mL of USP Alprazolam RS in Diluent. [NOTE-The solution is stable for 48 h at room temperature when stored in closed containers.]

Sample solution: 25 µg/mL of Alprazolam in Diluent. Sonicate for about 1 min. [NOTE-The solution is stable for 48 h at room temperature when stored in closed containers.]

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 231 nm

Column: 4.6-mm x 25-cm; packing L1

Column temperature: 40°

Flow rate: 1 mL/min

Injection size: 20 μL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of alprazolam (C₁₇H₁₃CIN₄) in the portion of Alprazolam taken:

Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak area from the Sample solution

r_S = peak area from the Standard solution

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

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

Acceptance criteria: 98.0%-102.0%

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.5%

4.2 ORGANIC IMPURITIES

Diluent, Buffer, Mobile phase, and Chromatographic system: Proceed as directed in the Assay.

System suitability solution: 20 µg/mL each of USP Alprazolam RS, USP Alprazolam Related Compound A RS, and USP 2-Amino-5-chlorobenzophenone RS in Diluent

Standard solution: 0.25 µg/mL of USP Alprazolam RS in Diluent. [NOTE-When stored in closed containers, the solution is stable for 48 h at room temperature.]

Sample solution: 250 µg/mL of Alprazolam in Diluent. Sonicate for about 1 min. [NOTE-When stored in closed containers, the Sample solution is stable for 24 h at room temperature.]

4.2.1 System suitability

Samples: Standard solution and System suitability solution

[NOTE-For relative retention times, see Table 1.]

Suitability requirements

Resolution: NLT 2.0 between alprazolam related compound A and alprazolam, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

4.2.2 Analysis

Samples: Standard solution and Sample solution

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

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

r_U = peak response for each impurity in the Sample solution

r_S = peak response for alprazolam from the Standard solution

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

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

F = relative response factor (see Table 1)

Acceptance criteria: See Table 1.

Table 1

5 SPECIFIC TESTS

LOSS ON DRYING (731): Dry a sample at 105° for 1 h: it loses NMT 0.5% of its weight.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, and store at controlled room temperature.

USP REFERENCE STANDARDS (11)

USP Alprazolam RS

USP Alprazolam Related Compound A RS

2-(2-Acetylhydrazino)-7-chloro-5-phenyl-3H-1,4-benzodiazepine.

USP 2-Amino-5-chlorobenzophenone RS

2-Amino-5-chlorobenzophenone.

C₁₃H₁₀CINO 231.68