Butylated Hydroxyanisole

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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C₁₁H₁₆O₂       180.24

Phenol, (1,1-dimethylethyl)-4-methoxy-;

tert-Butyl-4-methoxyphenol CAS RN®: 25013-16-5.

1 DEFINITION

Butylated Hydroxyanisole is predominantly 3-tert-butyl-4-hydroxyanisole, with varying amounts of 2-tert-butyl-4-hydroxyanisole. It contains NLT 98.5% of butylated hydroxyanisole (C₁₁H₁₆O₂) as a sum of the two isomers.

2 IDENTIFICATION

Change to read:

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

Analysis: Determine the position of the most intense 3-tert-butyl-4-hydroxyanisole peaks within 10 cm–1 of 682, 815, 855, 914, 1031, 1196, 1413, and 1504 cm–1 in a spectrum of USP 3-tert-Butyl-4-hydroxyanisole RS. Compare the peak positions of Butylated Hydroxyanisole to those of USP 3-tert-Butyl-4-hydroxyanisole RS.

Acceptance criteria: All peak positions determined from Butylated Hydroxyanisole are within 5 cm–1 of those determined from USP 3-tert Butyl-4-hydroxyanisole RS.

B.

Solution A: 5% acetic acid, prepared by diluting 50 mL of glacial acetic acid in a 1-L ask with water to volume Mobile phase: Acetonitrile and Solution A (65:35)

Standard solution: 0.4 mg/mL of USP 3-tert-Butyl-4-hydroxyanisole RS and 0.1 mg/mL of USP 2-tert-Butyl-4-hydroxyanisole RS in Mobile phase

Sample solution: 0.5 mg/mL of Butylated Hydroxyanisole in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 275 nm

Column: 3.0-mm × 15-cm; 3-µm packing L1

Column temperature: 40°

Flow rate: 0.75 mL/min

Injection volume: 10 µL

Run time: NLT 15 min

Analysis

Samples: Standard solution and Sample solution

[Note—2-tert-Butyl-4-hydroxyanisole and 3-tert-butyl-4-hydroxyanisole coelute under these chromatographic conditions. However, a small shoulder of 2-tert-butyl-4-hydroxyanisole may be seen on the left-hand side of the 3-tert-butyl-4-hydroxyanisole peak. The retention time of the 3-tert-butyl-4-hydroxyanisole peak is about 2.1 min.]

Acceptance criteria: The retention time of the main peak of the Sample solution corresponds to that of the Standard solution. The chromatographic prole of the Sample solution should be similar to that of the Standard solution and exhibit only 1 major peak corresponding to butylated hydroxyanisole.

3 ASSAY

Change to read:

Procedure

Solution A: Prepare as directed in Identication B.

Mobile phase: Acetonitrile and Solution A (45:55)

System suitability solution: (NF 1-May-2019) 90 µg/mL of USP 3-tert-Butyl-4-hydroxyanisole RS and 10 µg/mL of USP 2-tert-Butyl-4- hydroxyanisole RS in Mobile phase

Standard solution A: 90 µg/mL of USP 3-tert-Butyl-4-hydroxyanisole RS in Mobile phase

Standard solution B: 10 µg/mL of USP 2-tert-Butyl-4-hydroxyanisole RS in Mobile phase (NF 1-May-2019)

Sample solution: 100 µg/mL of Butylated Hydroxyanisole in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 290 nm

Column: 4.6-mm × 75-mm; 3.5-µm packing L1

Column temperature: 30°

Flow rate: 1.2 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution, Standard solution A, and Standard solution B (NF 1-May-2019)

[Note—The retention times of 2-tert-butyl-4-hydroxyanisole and 3-tert-butyl-4-hydroxyanisole are about 4.2 and 4.6 min, respectively.] Suitability requirements

Resolution: NLT 1.5 between the 3-tert-butyl-4-hydroxyanisole isomer and 2-tert-butyl-4-hydroxyanisole isomer peaks, System suitability solution (NF 1-May-2019)

Tailing factor: NMT 1.5, Standard solution A and Standard solution B (NF 1-May-2019)

Relative standard deviation: NMT 2.0% for the 3-tert-butyl-4-hydroxyanisole isomer and 2-tert-butyl-4-hydroxyanisole isomer peaks,

Standard solution A and Standard solution B (NF 1-May-2019)

Analysis

Samples: Standard solution A, Standard solution B, (NF 1-May-2019) and Sample solution

Measure the peak areas for each isomer.

Calculate the percentage of each isomer in the portion of Butylated Hydroxyanisole taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

= peak area of the corresponding isomer from the Sample solution

= peak area of the corresponding isomer from Standard solution A or Standard solution B (NF 1-May-2019)

= concentration of the appropriate Reference Standard in Standard solution A or Standard solution B (NF 1-May-2019) (µg/mL)

= concentration of Butylated Hydroxyanisole in the Sample solution (µg/mL)

[Note—Calculate the percentage of butylated hydroxyanisole (C₁₁H₁₆O₂) in the portion of Butylated Hydroxyanisole taken by adding the quantities of the two isomers.]

Acceptance criteria: NLT 98.5%

4 IMPURITIES

Residue on Ignition 〈281〉

Sample: 10 g

Acceptance criteria: NMT 0.01%

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers.

USP Reference Standards 〈11〉

USP 2-tert-Butyl-4-hydroxyanisole RS        C₁₁H₁₆O₂       180.25

USP 3-tert-Butyl-4-hydroxyanisole RS        C₁₁H₁₆O₂       180.25