Triazolam

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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C₁₇H₁₂Cl₂N₄          343.21

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

8-Chloro-6-(o-chlorophenyl)-1-methyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine CAS RN: 28911-01-5; UNII: 1HM943223R.

1 DEFINITION

Triazolam contains NLT 97.0% and NMT 103.0% of C₁₇H₁₂Cl₂N₄, calculated on the dried basis.

CAUTION-Exercise care to prevent inhaling particles of triazolam and to prevent its contacting any part of the body.]

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197MA _{(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

Diluent: Acetonitrile and water (45:55)

Buffer: 1.4 g/L monobasic potassium phosphate in water

Mobile phase: Acetonitrile and Buffer (45:55)

System suitability solution: 0.02 mg/mL each of USP Triazolam RS and USP Alprazolam Related Compound A RS in Diluent

Standard solution: 0.025 mg/mL of USP Triazolam RS in Diluent

Sample solution: 0.025 mg/mL of Triazolam in Diluent

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 215 nm

Column: 4.6-mm x 15-cm; 3.5-µm packing L1

Column temperature: 40°

Flow rate: 1 mL/min

Injection size: 10 µL

Run time: 3 times the retention time of triazolam

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for alprazolam related compound A and triazolam are 0.77 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 4.0 between alprazolam related compound A and triazolam, System suitability solution

Tailing:

NMT 1.5, Standard solution

Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of triazolam (C₁₇H₁₂Cl₂N₄) in the portion of Triazolam taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of triazolam from the Sample solution

r_s = peak response of triazolam from the Standard solution

C_s = concentration of USP Triazolam RS in the Standard solution (mg/mL)

C_u = concentration of Triazolam in the Sample solution (mg/mL)

Acceptance criteria: 97.0%–103.0% on the dried basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.5%

ORGANIC IMPURITIES

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

Standard solution: 0.25 µg/ml. of USP Triazolam RS in Diluent

Sample solution: 0.25 mg/mL of Triazolam in Diluent

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for alprazolam related compound A and triazolam are 0.77 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 4.0 between alprazolam related compound A and triazolam, System suitability solution

Tailing: NMT 1.5, Standard solution

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Sample: Sample solution

Calculate the total percentage of impurities in the portion of Triazolam taken:

Result = (r_u /r_T ) × 100

r_u = sum of the areas of each of the minor component peaks detected

r_T = sum of all minor component peak areas and the area of the major component peak

Acceptance criteria

Total impurities: NMT 1.5%

5 SPECIFIC TESTS

Loss on Drying 〈731〉: Dry a sample at 60° and at a pressure not exceeding 5 mm of mercury for 16 h: it loses NMT 0.5% of its weight.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers at room temperature.

USP Reference Standards 〈11〉

USP Triazolam RS

USP Alprazolam Related Compound A RS

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

C₁₇H₁₅ClN₄O 326.78