Metolazone 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

Metolazone Compounded Oral Suspension contains NLT 90.0% and NMT 110.0% of the labeled amount of metolazone (C₁₆H₁₆ClN₃O₃S).

Prepare Metolazone Compounded Oral Suspension 1 mg/mL as follows (see Pharmaceutical Compounding—Nonsterile Preparations 〈795〉).

Metolazone 100 mg

Vehicle: a 1:1 mixture of Vehicle for Oral Solution, (regular or sugar-free), NF, and Vehicle for Oral Suspension, NF, a sufficient quantity

to make 100 mL

Place the required number of tablets in a suitable mortar and comminute to a fine powder, or use Metolazone powder. Add 20 mL of Vehicle,

and mix to a uniform paste. Add the Vehicle in small portions, and transfer the contents of the mortar, stepwise and quantitatively, to a

calibrated bottle. Add Vehicle in portions to rinse the mortar, then add sufficient Vehicle to bring to final volume, and mix well.

2 ASSAY

Procedure

Mobile phase: Methanol and water (70:30) containing 1.5 g/L of ammonium acetate and 1 mL/L of diisopropylamine. Filter, and degas.

Standard solution: 1.0 µg/mL of USP Metolazone RS

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° until analyzed. At the time of analysis, remove the sample from the freezer, allow it to reach room temperature, and mix on a

vortex mixer for 30 s. Pipet 1.0 mL of the sample to a 1000-mL volumetric flask, and dilute with Mobile phase to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm × 20-cm; 5-µm packing L3

Flow rate: 1.0 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

[Note—The retention time for metolazone is about 6.0 min.]

Suitability requirements

Relative standard deviation: NMT 2.2% for replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of metolazone (C₁₆H₁₆ClN₃O₃S) in the portion of Oral Suspension taken:

Result = (r₁ / r₂) × (C₁ / C₂) × 100

r₁ = peak response from the Sample solution

r₂ = peak response from the Standard solution

C₁ = concentration of USP Metolazone RS in the Standard solution (µg/mL)

C₂ = nominal concentration of metolazone 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, and to state the Beyond-Use Date.

USP Reference Standards 〈11〉

USP Metolazone RS