Clonazepam Orally Disintegrating Tablets

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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1 DEFINITION

Clonazepam Orally Disintegrating Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of clonazepam (C₁₅H₁₀ClN₃O₃).

2 IDENTIFICATION

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

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

3 ASSAY

3.1 Procedure

Mobile phase: Acetonitrile, methanol, and water (25:25:50)

Standard solution: 0.01 mg/mL of USP Clonazepam RS in Mobile phase

Sample solution: Nominally 0.01 mg/mL of clonazepam in Mobile phase prepared as follows. Transfer an equivalent to about 2 mg of clonazepam, from finely powdered Tablets (NLT 20), to a 200-mL volumetric flask. Add 120 mL of Mobile phase and sonicate for about 15 min with intermittent shaking. Shake the flask on a mechanical shaker for about 30 min. Dilute with Mobile phase to volume. Pass a portion of this solution through a nylon membrane filter of 0.45-µm or finer pore size. Use the filtrate after discarding the first 4 mL. This solution is stable for 48 h at room temperature.

Chromatographic system

• (See Chromatography (621), System Suitability.)
• Mode: LC
• Detector: UV 254 nm. For Identification B, use a diode array detector in the range of 210–400 nm.
• Column: 4.6-mm × 15-cm; 5-µm packing L7
• Column temperature: 30°
• Flow rate: 1.2 mL/min
• Injection volume: 60 µL

System suitability

• Sample: Standard solution
• Suitability requirements
• Column efficiency: NLT 2000 theoretical plates
• Tailing factor: NMT 2.0
• Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of clonazepam (C₁₅H₁₀ClN₃O₃) in the portion of Tablets taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of clonazepam from the Sample solution

r_s = peak response of clonazepam from the Standard solution

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

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

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

4.1 Disintegration 〈701〉: NMT 60 s

4.2 Dissolution 〈711〉

Medium: Water; 900 mL, deaerated

Apparatus 2: 50 rpm

Time: 60 min

Mobile phase, Chromatographic system, and System suitability: Proceed as directed in the Assay except for Injection volume.

Injection volume: 100 µL

Standard stock solution: 0.01 mg/mL of USP Clonazepam RS in Mobile phase

Standard solution: Dilute the Standard stock solution with Medium according to the Tablet strength. See Table 1 for the concentration of the Standard solution corresponding to each Tablet strength.

Sample solution: Pass a portion of the solution under test through a nylon membrane filter of 0.45-µm pore size, discarding the first few milliliters.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of clonazepam (C₁₅H₁₀ClN₃O₃) dissolved:

Result = (r_u/r_s) × C_s × V × (1/L) × 100

r_u = peak response of clonazepam from the Sample solution

r_s = peak response of clonazepam from the Standard solution

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

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of clonazepam (C₁₅H₁₀ClN₃O₃) is dissolved.

4.3 Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

5.1 Organic Impurities

Mobile phase: Proceed as directed in the Assay.

System suitability solution: 0.2 µg/mL each of USP Clonazepam Related Compound A RS and USP Clonazepam Related Compound B RS in Mobile phase

Standard stock solution: Use the Standard solution from the Assay.

Standard solution: 0.2 µg/mL of USP Clonazepam RS from the Standard stock solution in Mobile phase

Sample solution: Nominally 0.1 mg/mL of clonazepam from Tablets prepared as follows. Transfer an equivalent to about 2 mg of clonazepam, from finely powdered Tablets (NLT 20), to a 50-mL volumetric flask. Pipet 20.0 mL of Mobile phase into the flask, and sonicate for about 2 min with intermittent shaking. Do not dilute to volume. Shake the flask for 30 min on a mechanical shaker. Pass a portion of this solution through a nylon membrane filter of 0.45-µm or finer pore size, and use the filtrate after discarding the first 4 mL.

Chromatographic system: Proceed as directed in the Assay except for Injection volume.

• Injection volume: 100 µL
• Run time: NLT 4 times the retention time of clonazepam

System suitability

• Samples: System suitability solution and Standard solution
• Suitability requirements
• Resolution: NLT 2.0 between clonazepam related compound A and clonazepam related compound B, System suitability solution
• Tailing factor: NMT 2.0, Standard solution
• Relative standard deviation: NMT 6.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

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

Result = (r_u/r_s) × (C_s/C_u) × (1/F) × 100

r_u = peak response of each impurity from the Sample solution

r_s = peak response of clonazepam from the Standard solution

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

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

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. Disregard any peaks with a relative retention time less than 0.63.

6 ADDITIONAL REQUIREMENTS

6.1 Packaging and Storage

Preserve in well-closed, light-resistant containers, and store at controlled room temperature.

6.2 USP Reference Standards 〈11〉

USP Clonazepam RS

USP Clonazepam Related Compound A RS

3-Amino-4-(2-chlorophenyl)-6-nitrocarbostyril.

C₁₅H₁₀ClN₃O₃ 315.72

USP Clonazepam Related Compound B RS

2-Amino-2′-chloro-5-nitrobenzophenone.

C₁₃H₉ClN₂O₃ 276.68