Butylated Hydroxytoluene

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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C₁₅H₂₄O 220.35

Phenol, 2,6-bis(1,1-dimethylethyl)-4-methyl-;

2,6-Di-tert-butyl-p-cresol CAS RN®: 128-37-0.

1 DEFINITION

Butylated Hydroxytoluene contains NLT 99.0% and NMT 101.5% of butylated hydroxytoluene (C H O).

2 IDENTIFICATION

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

Sample: Undried sample

Acceptance criteria: Meets the requirements

B. The retention time of the butylated hydroxytoluene peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. The chromatographic prole of the Sample solution should exhibit only one major peak corresponding to the main compound.

3 ASSAY

3.1 Procedure

Solution A: 5% acetic acid, prepared by diluting 50 mL of glacial acetic acid in a 1-L flask with water to volume

Mobile phase: Acetonitrile and Solution A (65:35)

Standard solution: 0.5 mg/mL of USP Butylated Hydroxytoluene RS in Mobile phase

Sample solution: 0.5 mg/mL of Butylated Hydroxytoluene 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: 15 min

3.2 System suitability

Sample: Standard solution

[Note—The retention time of butylated hydroxytoluene is about 10.8 min.]

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 0.5%

3.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of butylated hydroxytoluene (C H O) in the portion of Butylated Hydroxytoluene taken:

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

r_U = peak area of butylated hydroxytoluene from the Sample solution

r_S = peak area of butylated hydroxytoluene from the Standard solution

C_S = concentration of USP Butylated Hydroxytoluene RS in the Standard solution (mg/mL)

C_U = concentration of Butylated Hydroxytoluene in the Sample solution (mg/mL)

Acceptance criteria: 99.0%–101.5%

4 IMPURITIES

Change to read:

4.1 Residue on Ignition 〈281〉

Sample: 50 g

Analysis: Transfer the Sample to a tared crucible, heat gently at a temperature as low as practicable until the Sample is thoroughly charred, (NF 1-May-2021) and cool. Moisten the ash with 1 mL of sulfuric acid, and complete the ignition by heating at 800 ± 25° for 15-min periods to constant weight.

Acceptance criteria: NMT 0.002%

4.2 Organic Impurities

Mobile phase and Chromatographic system: Proceed as directed in the Assay, except extend the Run time to 20 min.

Standard solution: 2 μg/mL of USP Butylated Hydroxytoluene RS in Mobile phase

Sample solution: 2.0 mg/mL of Butylated Hydroxytoluene in Mobile phase

System suitability

Sample: Standard solution

[Note—The retention time of butylated hydroxytoluene is about 10.8 min.]

Suitability requirements

Signal-to-noise ratio: NLT 40

Analysis

Samples: Standard solution and Sample solution

Calculate the corrected peak area of each individual impurity in the Sample solution:

Result = r_U/F

r_U = peak area of the individual impurity from the Sample solution

F = relative response factor (see Table 1)

Acceptance criteria

Individual impurity: NMT 0.1%; the corrected peak area of each impurity in the Sample solution is NMT the area of the principal peak in the Standard solution.

Total impurities: NMT 0.7%; the sum of all the corrected peak areas due to impurities in the Sample solution, excluding the butylated hydroxytoluene peak area, is NMT 7 times the butylated hydroxytoluene peak area in the Standard solution.

Table 1

^a The p-cresol and m-cresol peaks are not separated under the method conditions.

^b The 2-tert-butyl-4-methylphenol and 2-tert-butyl-5-methylphenol peaks are not separated under the method conditions.

5 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers.

USP Reference Standards 〈11〉

USP Butylated Hydroxytoluene RS