Adipic Acid

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

Adipic Acid contains NLT 98.0% and NMT 102.0% of adipic acid (C₆H₁₀O₄), calculated on the dried basis.

2 IDENTIFICATION

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K

B. The retention time of the adipic acid peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

PROCEDURE

Solution A: 6.8 mL of 85% phosphoric acid in 4000 mL of water

Solution B: Acetonitrile

Mobile phase: See Table 1.

Re-equilibrate the column at the initial Mobile phase composition before the next injection.

Diluent: Acetonitrile and Solution A (3:97)

Standard solution: 0.5 mg/mL of USP Adipic Acid RS in Diluent

Sample solution: 0.5 mg/mL of Adipic Acid in Diluent

Chromatographic system

(See Chromatography (621), System Suitability)

Mode: LC

Detector: UV 209 nm

Column: 4.6-mm × 15-cm; 3-µm packing L1

Column temperature: 40°

Flow rate: 1.0 mL/min

Injection volume: 30 µL

System suitability

Sample: Standard solution

Suitability requirements

 Tailing factor: NMT 2.0

 Relative standard deviation: NMT 0.7%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of adipic acid (C₆H₁₀O₄) in the portion of Adipic Acid taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak area of adipic acid from the Sample solution

rₛ = peak area of adipic acid from the Standard solution

Cₛ = concentration of USP Adipic Acid RS in the Standard solution (mg/mL)

Cᵤ = concentration of Adipic Acid in the Sample solution (mg/mL)

Acceptance criteria: 98.0%-102.0% on the dried basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281): NMT 0.1%

4.2 LIMIT OF NITRATES

Standard stock solution: 1.63 mg/mL of potassium nitrate

Standard solution: Dilute 1 mL of the Standard stock solution with water to 10 mL. Dilute 1 mL of this solution with water to 50 mL to obtain a solution containing 2 µg/mL of nitrate.

Sample solution: Transfer 5 g of Adipic Acid to a 50-mL volumetric flask. Dissolve in water, with heating, and dilute with water to volume. Allow to cool and crystallize and then pass through a sintered-glass filter. Wash the filter with water, and collect the filtrate and washings until a volume of 50 mL is obtained. [Note—This solution is also to be used for Chloride, Sulfate, and Iron.]

Control: 2 mg/L of potassium permanganate

Analysis: Transfer 1.0 mL of the Sample solution, 1.5 mL of the Standard solution, and 1 mL of water (blank) to three separate flasks. To each flask add 2 mL of ammonium hydroxide, 0.5 mL of 10 mg/mL manganese sulfate, and 1 mL of 10 mg/mL sulfanilamide, and dilute each solution with water to 20 mL. Add 100 mg of zinc powder to each of the three flasks, and cool in an ice bath for 30 min, shaking the solutions periodically. Separately filter 10 mL of each solution, cool in an ice bath, and then add 2.5 mL of hydrochloric acid and 1 mL of 10 mg/mL of naphthylethylenediamine dihydrochloride. Allow the solutions to stand at room temperature for 15 min.

System suitability: The test is invalid if the concomitantly prepared blank solution is darker than the Control.

Acceptance criteria: No discernible color, indicating that the Sample solution is not darker than the concomitantly prepared solution containing the Standard solution (NMT 30 ppm).

4.3 CHLORIDE AND SULFATE (221), Chloride

Sample: A 5-mL portion of the Sample solution from Limit of Nitrates

Analysis: Proceed as directed in the chapter.

Acceptance criteria: The Sample shows no more chloride than a corresponding 0.14-mL portion of 0.020 N hydrochloric acid (NMT 0.02%).

4.4 CHLORIDE AND SULFATE (221), Sulfate

Sample: A 5-mL portion of the Sample solution from Limit of Nitrates

Analysis: Proceed as directed in the chapter.

Acceptance criteria: The Sample shows no more sulfate than a corresponding 0.26-mL portion of 0.020 N sulfuric acid (NMT 0.05%).

4.5 IRON (241)

Sample: A 10-mL portion of the Sample solution from Limit of Nitrates

Analysis: Proceed as directed in the chapter.

Acceptance criteria: NMT 10 ppm

Change to read:

4.6 RELATED SUBSTANCES

Solution A, Solution B, Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 5 µg/mL of USP Adipic Acid RS

Sample solution: 5 mg/mL of Adipic Acid in Diluent

System suitability

Sample: Standard solution

[Note—See Table 2 for the relative retention times.]

Suitability requirements

 Tailing factor: NMT 2.0

 Relative standard deviation: NMT 5.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each individual impurity, excluding any solvent peaks, in the portion of Adipic Acid taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × (1/Fᵣ) × F꜀ × 100

rᵤ = peak area of each individual impurity from the Sample solution

rₛ = peak area of adipic acid from the Standard solution

Cₛ = concentration of USP Adipic Acid RS in the Standard solution (µg/mL)

Cᵤ = concentration of Adipic Acid in the Sample solution (mg/mL)

Fᵣ = relative response factor from Table 2 for known impurities (use Fᵣ = 1 for unknown impurities)

F꜀ = conversion factor, 0.001 mg/µg (µg to mg)

Acceptance criteria

 Individual impurity: NMT 0.1%

 Total impurities: NMT 0.5%

5 SPECIFIC TESTS

MELTING RANGE OR TEMPERATURE (741): 151°–154°

LOSS ON DRYING (731): Dry a sample at 105° for 3 h; it loses NMT 0.2% of its weight.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in a tight container. No storage requirements are specified.

USP REFERENCE STANDARDS (11)

USP Adipic Acid RS