Acetylcysteine 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 Solution is a sterile solution of Acetylcysteine in water, prepared with the aid of Sodium Hydroxide. It contains NLT 90.0% and NMT 110.0% of the labeled amount of acetylcysteine (C₅H₉NO₃S).

2 IDENTIFICATION

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A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K (CN 1-May-2020)

Sample solution: Place 10 mL in a suitable beaker, and adjust to a pH of 2 (pH indicator paper), using 3 N hydrochloric acid. Add up to 2 g of finely powdered sodium chloride, in two portions of 200 mg each initially and then in smaller portions of 25 mg, stirring after each addition until the sodium chloride dissolves and a precipitate is formed. The precipitate appears as a very fine powder, and the solution turns cloudy. If no precipitate forms, add an additional drop of 3 N hydrochloric acid, and stir until the precipitate forms. Allow to stand at room temperature for 15 min, and collect the residue by suction filtration. Use the acetylcysteine so obtained after being dried at a pressure of 50mm of mercury at 70° for 4 h.

Acceptance criteria: Meets the requirements

3 ASSAY

3.1 Procedure

Solution A: 0.5 mg/mL of sodium metabisulfite solution in water, freshly prepared

Solution B: 0.5 mg/mL of sodium bisulfite solution

Mobile phase: 6.8 g/L of monobasic potassium phosphate. Adjust with phosphoric acid to a pH of 3.0.

Internal standard solution: 5 mg/mL of USP l-Phenylalanine RS in Solution A

Standard stock solution: 10 mg/mL of USP Acetylcysteine RS in Solution A

Standard solution: 0.5 mg/mL of USP Acetylcysteine RS and 0.25 mg/mL of USP l-Phenylalanine RS in Solution A from Standard stock solution and Internal standard solution

Sample stock solution: Equivalent to 10 mg/mL of acetylcysteine from the volume of Solution in Solution B

Sample solution: 0.5 mg/mL of acetylcysteine and 0.25 mg/mL of USP l-Phenylalanine RS in Solution A from Sample stock solution and Internal standard solution

3.2 Chromatographic system

Mode: LC

Detector: UV 214 nm

Column: 3.9-mm × 30-cm; packing L1

Flow rate: 1.5 mL/min

Injection volume: 5 μL

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Resolution: NLT 6 between acetylcysteine and l-phenylalanine

Relative standard deviation: NMT 2.0%

3.5 Analysis

Samples: Standard solution and Sample solution

[Note - The relative retention times for acetylcysteine and l-phenylalanine are about 0.5 and 1.0, respectively.]

Calculate the percentage of the labeled amount of acetylcysteine (C H NO S) in the portion of Solution taken:

Result = (R_u/R_s) × (C_s/C_u) × 100

R_u = peak response ratio of acetylcysteine to l-phenylalanine from the Sample solution

R_s = peak response ratio of acetylcysteine to l-phenylalanine 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%

4 SPECIFIC TESTS

pH 〈791〉: 6.0–7.5

Sterility Tests 〈71〉: Meets the requirements

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-unit or multiple-unit tight containers that effectively exclude oxygen, and store at controlled room temperature.

USP Reference Standards 〈11〉

USP Acetylcysteine RS

USP l-Phenylalanine RS