Clonazepam Compounded Oral Suspension

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 Compounded Oral Suspension contains NLT 90.0% and NMT 110.0% of the labeled amount of clonazepam (C₁₅H₁₀ClN₃O₃). Prepare Clonazepam Compounded Oral Suspension 0.1 mg/mL as follows (see Pharmaceutical Compounding-Nonsterile Preparations 〈795〉):

If using tablets, comminute the tablets into a fine powder in a suitable mortar, or add Clonazepam powder to the mortar. Add approximately 10 mL of the Vehicle, and mix to a uniform paste. Add the Vehicle in small portions almost to volume, and mix thoroughly after each addition. Transfer the contents of the mortar, stepwise and quantitatively, to a calibrated bottle. Add enough Vehicle to bring to final volume, and mix well.

2 ASSAY

2.1 Procedure

Mobile phase: Methanol, acetonitrile, and water (30:30:40). Filter and degas.

Standard solution: 25 µg/mL of USP Clonazepam RS in acetonitrile

Sample solution: Agitate the container of Oral Suspension for 30 min on a rotating mixer, remove a 5-mL sample, and store in a clear glass vial at −70°C until analyzed. At the time of analysis, remove the sample from the freezer, allow it to reach room temperature, and mix with a vortex mixer for 30 s. Pipet 2.5 mL of the sample into a 10-mL volumetric flask, and dilute with acetonitrile to volume to obtain a solution having a nominal concentration of 25 µg/mL of clonazepam.

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 254 nm
• Column: 4.6-mm × 10-cm; 5-µm packing L1
• Flow rate: 1 mL/min
• Injection volume: 20 µL

System suitability

• Sample: Standard solution
• [Note-The retention time for clonazepam is about 7 min.]
• Suitability requirements
• Relative standard deviation: NMT 1.8% for replicate injections

Analysis

Samples: Standard solution and Sample solution

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

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response from the Sample solution

r_s = peak response from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

3 SPECIFIC TESTS

pH 〈791〉: 3.6–4.6

4 ADDITIONAL REQUIREMENTS

Packaging and Storage: Package in tight, light-resistant containers. Store at controlled room temperature or in a refrigerator.

Beyond-Use Date: NMT 60 days after the date on which it was compounded when stored at controlled room temperature or in a refrigerator

Labeling: Label it to state that it is to be well shaken before use, and to state the Beyond-Use Date.

USP Reference Standards 〈11〉

USP Clonazepam RS