Mandelic 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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C₈H₈O₃             152.15

Benzeneacetic acid, α-hydroxy-;

(RS)-2-Hydroxy-2-phenylacetic acid;

(±)-α-Hydroxyphenylacetic acid;

2-Hydroxy-2-phenylacetic acid CAS RN®: 90-64-2.

1 DEFINITION

Mandelic Acid contains NLT 98.0% and NMT 102.0% of α-hydroxyphenylacetic acid (C₈H₈O₃), calculated on the anhydrous basis.

2 IDENTIFICATION

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197K

B. Chromatographic Identity

Analysis: Proceed as directed in the Assay.

Acceptance criteria: The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Solvent A: 0.01 M phosphoric acid

Mobile phase: Acetonitrile, methanol, and Solvent A (17:3:80)

Standard stock solution A: Prepare a solution having known concentrations of 0.2 mg/mL of acetophenone, 0.5 mg/mL of benzoylformic acid, and 0.25 mg/mL of USP Benzaldehyde RS, respectively, in Mobile phase.

Standard stock solution B: Transfer 25 mg of USP Benzoic Acid RS to a 250-mL volumetric ask, add 5.0 mL of Standard stock solution A, dilute with Mobile phase to volume, and mix.

Standard stock solution C: Use USP Mandelic Acid RS to prepare a solution having a known concentration of 5 mg/mL in Mobile phase. System suitability solution: Transfer 5.0 mL of Standard stock solution B and 20.0 mL of Standard stock solution C to a 100-mL volumetric ask, dilute with Mobile phase to volume, and mix. The solution contains 1 mg/mL of USP Mandelic Acid RS, 0.2 µg/mL of acetophenone, 0.5 µg/mL of benzoylformic acid, 0.25 µg/mL of USP Benzaldehyde RS, and 5 µg/mL of USP Benzoic Acid RS. Standard solution: 1 mg/mL of USP Mandelic Acid RS in Mobile phase prepared from Standard stock solution C Sample solution: 1 mg/mL of Mandelic Acid in Mobile phase

3.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temperature: Ambient

Flow rate: 0.8 mL/min

Injection volume: 20 µL

3.2 System suitability

Sample: System suitability solution

[Note—See Table 1 for relative retention times.]

Table 1

Suitability requirements

Resolution: NLT 3.0, between the benzoylformic acid peak and the mandelic acid peak and between the benzoic acid peak and the benzaldehyde peak

Relative standard deviation: NMT 1% for the mandelic acid peak

Tailing factor: NMT 2.0 for each peak

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of mandelic acid (C₈H₈O₃) in the portion of Mandelic Acid taken:

Result = (r_U /r_S ) × (C_S /C_U ) × 100

r_U = peak response of mandelic acid from the Sample solution

r_S = peak response of mandelic acid from the Standard solution

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

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

Acceptance criteria: 98.0%–102.0% on the anhydrous basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Limit of Benzoylformic Acid, Benzaldehyde, Benzoic Acid, and Acetophenone

Standard stock solution A, Standard stock solution B, Chromatographic system, and System suitability: Proceed as directed in the Assay. Standard solution: Transfer 5.0 mL of Standard stock solution B to a 100-mL volumetric ask, dilute with Mobile phase to volume, and mix. The Standard solution contains 0.2 µg/mL of acetophenone, 0.5 µg/mL of benzoylformic acid, 0.25 µg/mL of USP Benzaldehyde RS, and 5 µg/mL of USP Benzoic Acid RS.

Sample solution: 2.5 mg/mL of Mandelic Acid in Mobile phase

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each related compound (benzoylformic acid, benzaldehyde, benzoic acid, or acetophenone) in the portion of Mandelic Acid taken:

Result = (r_U /r_S ) × (C_S /C_U) × 100

U S S U

r_U = peak response of the relevant related compound (benzoylformic acid, benzaldehyde, benzoic acid, or acetophenone) from the Sample solution

r_S = peak response of the relevant related compound (benzoylformic acid, benzaldehyde, benzoic acid, or acetophenone) from the  Standard solution

C_S = concentration of the relevant related compound (benzoylformic acid, USP Benzaldehyde RS, USP Benzoic Acid RS, or acetophenone) in the Standard solution (mg/mL)

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

Acceptance criteria

Benzoylformic acid: NMT 0.1%

Benzoic acid: NMT 1.0%

Benzaldehyde: NMT 0.05%

Acetophenone: NMT 0.01%

Limit of Chloride

Sample: 1 g

Analysis: Proceed as directed for Chloride and Sulfate 〈221〉, Chloride.

Acceptance criteria: 0.01%; a 1-g portion shows no more than corresponds to 0.15 mL of 0.020 N hydrochloric acid.

5 SPECIFIC TESTS

Melting Range or Temperature 〈741〉: 118°–121°

Water Determination, Method Ia 〈921〉: NMT 0.5%

Change to read:

Turbidity

(See Nephelometry and Turbidimetry 〈855〉.)

Sample solution: 50 mg/mL in water

Blank: Reserve a portion of the water used to prepare the Sample solution.

Fixed reproducible standards: See Determination of Turbidity in Elastomeric Components Used in Injectable Pharmaceutical Packaging/Delivery Systems 〈381〉 _{(CN 1-Dec-2020)}.

Analysis: Measure the turbidity of the Sample solution and Blank as directed in Nephelometry and Turbidimetry 〈855〉 against the Fixed reproducible standards.

Acceptance criteria: The turbidity is the difference between the values obtained for the Blank and the Sample solution, expressed in Nephelos units. The Sample solution shows no more turbidity than the 10 Nephelos units standard.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers. Store in a dry and well-ventilated place. Protect from light.

USP Reference Standards 〈11〉

USP Benzaldehyde RS

USP Benzoic Acid RS

USP Mandelic Acid RS