Acetylcysteine Compounded Solution

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

Acetylcysteine Compounded Solution contains NLT 90.0% and NMT 110.0% of the labeled amount of acetylcysteine (C₅H₉NO₃S). Prepare

Acetylcysteine Compounded Solution 20% as follows (see Pharmaceutical Compounding - Sterile Preparations 〈797〉).

^a It is necessary to adjust the formula and compound an additional amount to completely fill each single-unit container to minimize exposure to oxygen because the preparation is susceptible to oxidation.

Dissolve Edetate Disodium Dihydrate in 7 mL of Sterile Water for Injection. Slight heating may be necessary. Allow to cool. Dissolve

Acetylcysteine in the edetate disodium solution. Add Sodium Hydroxide 10% Solution dropwise with mixing to adjust the pH to between 6.5 and 7.5. Bring to final volume with Sterile Water for Injection and mix well. Pass through a sterile filter of 0.22-μm pore size into single-unit sterile containers. It is necessary to completely fill the container to minimize the amount of oxygen present because the preparation is susceptible to oxidation.

2 ASSAY

Procedure

Mobile phase: Acetonitrile, phosphoric acid, and water (3:0.5:96.5)

Standard solution: 0.4 mg/mL of acetylcysteine prepared from USP Acetylcysteine RS in Mobile phase

Sample solution: Transfer 0.4 mL of Solution to a 200-mL volumetric flask, dilute with Mobile phase to volume, and mix well.

Chromatographic system

Mode: LC

Detector: UV 200 nm

Column: 4.6-mm × 25-cm; 5-μm packing L96

Column temperature: 15°

Flow rate: 2.0 mL/min

Injection volume: 10 μL

System suitability

Sample: Standard solution

[Note - The retention time for acetylcysteine is about 3.8 min.]

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0% for replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of acetylcysteine (C₅H₉NO₃S) in the portion of Solution taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of acetylcysteine from the Sample solution

r_s = peak response of acetylcysteine from the Standard solution

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

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

Acceptance criteria: 90.0%–110.0%

3 SPECIFIC TESTS

pH 〈791〉: 6.5–7.5

Sterility Tests 〈71〉, Test for Sterility of the Product to Be Examined, Membrane Filtration: Meets the requirements

4 ADDITIONAL REQUIREMENTS

Packaging and Storage: Package in single-unit sterile glass containers and store at controlled room temperature.

Change to read:

Beyond-Use Date: In the absence of performing and completing a sterility test, the storage conditions in Pharmaceutical Compounding – Sterile Preparations 〈797〉, 14.3 Establishing a BUD for a CSP apply.▲ (CN 1-Nov-2023) After successful completion of sterility testing, the Beyond-

Use Date is NMT 60 days after the date on which it was compounded when stored at controlled room temperature.

Labeling: Label it to state the Beyond-Use Date. The label indicates that the Solution is not to be used if it contains a precipitate. Label it to state that it is a single-unit container, that it is over filled with an excess that should be discarded after a measured single dose is used, and to store at controlled room temperature. Label it for inhalation or oral administration only. Label it to state that the preparation may have a disagreeable odor and light purple color that is a result of a chemical reaction that does not affect the strength of the preparation.

USP Reference Standards 〈11〉

USP Acetylcysteine RS