Malic 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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Hydroxybutanedioic acid, (±)-;

(±)-Malic acid;

(±)-Hydroxysuccinic acid CAS RN^®: 617-48-1.

1 DEFINITION

Malic Acid contains NLT 99.0% and NMT 100.5% of CHO

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K (CN 1-MAY-2020): On undried sample

3 ASSAY

3.1 PROCEDURE

Sample: 2 g

Titrimetric system

(See Titrimetry (541).)

Mode: Direct titration

Titrant: 1 N sodium hydroxide VS

Endpoint detection: Visual

Analysis: Dissolve the Sample in 40 mL of recently boiled and cooled water. Add phenolphthalein TS, and titrate to the first appearance of a faint pink color that persists for NLT 30 s. Perform a blank determination.

Calculate the percentage of malic acid (C₄H₆O₅) in the Sample taken:

Result = [(V - B) x N x F x 100]/W

V = volume of Titrant consumed by the Sample (mL)

B = volume of Titrant consumed by the Blank (mL)

N = actual normality of the Titrant (mEq/mL)

F = equivalency factor, 67.04 mg/mEq

W = weight of the Sample (mg)

Acceptance criteria: 99.0%-100.5%

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 FUMARIC AND MALEIC ACIDS

Mobile phase: 0.01 N sulfuric acid

System suitability solution: 1 mg/mL of Malic Acid, 10 µg/mL of USP Fumaric Acid RS, and 4 µg/mL of USP Maleic Acid RS in Mobile phase

Standard solution: 5.0 µg/mL of USP Fumaric Acid RS and 2.0 µg/mL of USP Maleic Acid RS in Mobile phase

Sample solution: 1.0 mg/mL of Malic Acid in Mobile phase

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 210 nm

Column: 6.5-mm x 30-cm; packing L17

Column temperature: 37 ± 1°

Flow rate: 0.6 mL/min

Injection size: 20 µL

System suitability

Sample: System suitability solution

[NOTE-The relative retention times for maleic acid, malic acid, and fumaric acid are 0.6, 1.0, and 1.5, respectively.]

Suitability requirements

Resolution: NLT 2.5 for the maleic acid and malic acid peaks; NLT 7.0 for the malic acid and fumaric acid peaks

Relative standard deviation: NMT 2.0% for the maleic acid peak

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of maleic acid and of fumaric acid in the portion of Malic Acid taken:

Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak response of maleic acid or fumaric acid from the Sample solution

r_S = peak response of maleic acid or fumaric acid from the Standard solution s

C_S = concentration of USP Maleic Acid RS or USP Fumaric Acid RS in the Standard solution (mg/mL)

C_U = concentration of Malic Acid in the Sample solution (mg/mL)

Acceptance criteria

Fumaric acid: NMT 1.0%

Maleic acid: NMT 0.05%

4.3 WATER-INSOLUBLE SUBSTANCES

Sample: 25 g

Analysis: Dissolve the Sample in 100 mL of water, filter the solution through a tared filtering crucible, wash the filter with hot water, and dry at 100° to constant weight.

Acceptance criteria: The increase in weight is NMT 25 mg (0.1%).

5 ADDITIONAL REQUIREMENTS

5.1 PACKAGING AND STORAGE

Preserve in well-closed containers.

5.2 USP REFERENCE STANDARDS (11)

USP Fumaric Acid RS

USP Maleic Acid RS

USP Malic Acid RS