Methimazole

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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1 DEFINITION

Methimazole contains NLT 98.0% and NMT 101.0% of methimazole (C₄H₆N₂S), calculated on the dried basis.

2 IDENTIFICATION

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

3 ASSAY

Procedure

Sample: 250 mg of Methimazole

Analysis: Dissolve the Sample in 75 mL of water. Add 15.0 mL of 0.1 N sodium hydroxide VS, mix, and add, with stirring, 30 mL of 0.1 N silver nitrate. Continue the titration with 0.1 N sodium hydroxide VS, determining the endpoint potentiometrically. Each milliliter of 0.1 N sodium hydroxide is equivalent to 11.42 mg of methimazole (C₄H₆N₂S).

Acceptance criteria: 98.0%–101.0% on the dried basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Delete the following:

Selenium 〈291〉

Sample: 200 mg of Methimazole

Acceptance criteria: NMT 30 ppm (USP 1-May-2022)

Change to read:

Organic Impurities

Standard solution: 0.01 mg/mL each of USP Methimazole RS, USP Methimazole Related Compound A RS, 1-methylimidazole, and USP

Methimazole Related Compound C RS in chloroform

Sample solution: 10 mg/mL of Methimazole in chloroform

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: GC

Detector: Flame ionization

Column: 30-m × 0.25-mm; coated with a 0.5-μm

lm of phase G27

Temperatures

Injection port: 150°

Detector: 250°

Column: See Table 1.

Table 1

Carrier gas: Helium

Flow rate: 1.5 mL/min

Injection volume: 1 μL

Injection type: Split, split ratio 3:20

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 1.5 between methimazole related compound A and 1-methylimidazole

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of methimazole related compound A, 1-methylimidazole, and methimazole related compound C in the portion of Methimazole taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each related compound from the Sample solution

r_S = peak response of the corresponding related compound from the Standard solution

C_S = concentration of the corresponding related compound in the Standard solution (mg/mL)

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

Calculate the percentage of any other individual impurity in the portion of Methimazole taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of methimazole from the Standard solution

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

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

Acceptance criteria: See Table 2. The reporting threshold is (USP 1-May-2022) 0.02%.

Table 2

5 SPECIFIC TESTS

Loss on Drying 〈731〉

Analysis: Dry at 105° for 2 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed, light-resistant containers.

USP Reference Standards 〈11〉

USP Methimazole RS

USP Methimazole Related Compound A RS

2,2-Dimethoxy-N-methylethanamine.

C₅H₁₃NO₂ 119.16

USP Methimazole Related Compound C RS

1-Methyl-2-(methylthio)-1H-imidazole.

C₅H₈N₂S 128.20