Denatonium Benzoate

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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C₂₈H₃₄N₂O₃ H₂O  464.60

C₂₈H₃₄N₂O₃  446.59

Benzenemethanaminium, N-[2-[(2,6-dimethylphenyl)amino]-2-oxoethyl]-N,N-diethyl-, benzoate, monohydrate;

Benzyldiethyl [(2,6-xylylcarbamoyl)methyl]ammonium benzoate monohydrate CAS RN^®: 86398-53-0.

Anhydrous CAS RN^®: 3734-33-6.

1 DEFINITION

Denatonium Benzoate, dried at 105° for 2 h , contains one molecule of water of hydration or is anhydrous. When dried at 105° for 2 h, it contains NLT 99.5% and NMT 101.0% of denatonium benzoate (C₂₈H₃₄N₂O₃).

2 IDENTIFICATION

Change to read:

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

Change to read:

2.2 B. SPECTROSCOPIC IDENTIFICATION TESTS (197), Ultraviolet-Visibl Ultraviolet-Visible Spectroscopy: 197U (CN 1-MAY-2020)

Analytical wavelength: 263 nm

Sample solution: 100 µg/mL

Medium: Water

Acceptance criteria: Absorptivities, calculated on the dried basis, do not differ by more than 3.0%.

2.3 C.

Sample: 150 mg

Analysis: Dissolve the Sample in 10 mL of water, and add 15 mL of trinitrophenol TS.

Acceptance criteria: A yellow precipitate is formed.

2.4 D.

Sample: 100 mg

Analysis: Dissolve the Sample in 10 mL of water, and add 20 mL of 2 N sulfuric acid and 15 mL of ammonium reineckate TS. Mix, filter through a sintered-glass crucible using gentle suction, and wash thoroughly with water. Remove as much water as possible with suction, and then dry in an oven at 105° for 1 h.

Acceptance criteria: The denatonium reineckate so obtained melts at about 170° (see Melting Range or Temperature (741)).

3 ASSAY

3.1 PROCEDURE

Sample: 900 mg, previously dried

Blank: 50 mL of glacial acetic acid

Titrimetric system

(See Titrimetry (541).)

Mode: Direct titration

Titrant: 0.1 N perchloric acid VS

Endpoint detection: Visual

Analysis: Dissolve the Sample in 50 mL of glacial acetic acid, and add 1 drop of crystal violet TS. Titrate with Titrant to a green endpoint.

Perform a blank determination, and make any necessary correction.

Calculate the percentage of denatonium benzoate (C₂₈H₃₄N₂O₃) in the portion of sample taken:

Result = {[(V_S - V_B) x N x F]/W) x 100

V_S = Titrant volume consumed by the Sample (mL)

V_B = Titrant volume consumed by the Blank (mL)

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

F = equivalency factor, 446.6 mg/mEq

W = Sample weight (mg)

Acceptance criteria: 99.5%-101.0% on the dried basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.1%

CHLORIDE AND SULFATE, Chloride (221)

Standard solution: 0.10 mL of 0.020 N hydrochloric acid

Sample soluton: Dissolve 350 mg in 9 mL of water, add 1 mL of nitric acid, and filter.

Analysis: Use 1.0 mL of the Sample solution, and proceed as directed in the chapter

Acceptance criteria: 0.2%; the Sample solution shows no more chloride than the Standard solution.

5 SPECIFIC TESTS

MELTING RANGE OR TEMPERATURE (741): 163°-170°, on a dried specimen

PH (791)

Sample solution: 30 mg/mL

Acceptance criteria: 6.5-7.5

LOSS ON DRYING (731)

Analysis: Dry at 105° for 2 h.

Acceptance criteria

Monohydrate form: 3.5%-4.5%

Anhydrous form: NMT 1.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

LABELING: Label it to indicate whether it is hydrous or anhydrous.

USP REFERENCE STANDARDS (11)

USP Denatonium Benzoate RS