Metyrapone

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

DOWNLOAD PDF HERE

C₁₄H₁₄N₂O         226.27

1-Propanone, 2-methyl-1,2-di-3-pyridinyl-;

2-Methyl-1,2-di-3-pyridyl-1-propanone CAS RN^®: 54-36-4; UNII: ZS9KD92H6V.

1 DEFINITION

Metyrapone contains NLT 98.0% and NMT 102.0% of metyrapone (C₁₄H₁₄N₂O), calculated on the dried basis. 

2 IDENTIFICATION

Change to read:

A. ^▲SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197M _{▲(CN 1-MAY-2020)}

Change to read:

B. ^▲SPECTROSCOPIC IDENTIFICATION TESTS (197), Ultraviolet-Visible Spectroscopy: 1970 _{▲(CN 1-MAY-2020)}

Sample solution: 10 µg/mL in 1 N sulfuric acid

Acceptance criteria: Meets the requirements

3 ASSAY

PROCEDURE

Diluent: 1 N sulfuric acid

Standard solution: 10 µg/mL of USP Metyrapone RS in Diluent

Sample solution: 10 µg/mL of Metyrapone in Diluent

Instrumental conditions

Mode: UV

Analytical wavelength: 260 nm

Cell: 1 cm

Blank: Diluent

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of metyrapone (C₁₄H₁₄N₂O) in the portion of Metyrapone taken:

                         Result = (A_U/A_S) × (C_S/C_U) × 100

A_U = absorbance of the Sample solution 

A_S = absorbance of the Standard solution

C_S = concentration of USP Metyrapone RS in the Standard solution (µg/mL)

C_U = concentration of Metyrapone in the Sample solution (µg/mL)

Acceptance criteria: 98.0%-102.0% on the dried basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 ORGANIC IMPURITIES

Standard stock solution: 0.2 mg/mL of USP Metyrapone RS in methanol

Standard solution A: 40 µg/mL of USP Metyrapone RS in methanol

Standard solution B: 20 µg/mL of USP Metyrapone RS in methanol

Sample solution: 20 mg/mL of Metyrapone in methanol

Chromatographic system

(See Chromatography (621), Thin-Layer Chromatography.)

Mode: TLC

Adsorbent: 0.25-mm layer of chromatographic silica gel mixture

Application volume: 5 µL

Developing solvent system: Chloroform and methanol (48:3)

Analysis

Samples: Standard stock solution, Standard solution A, Standard solution B, and Sample solution

Apply each of the Samples separately to the TLC plate. Position the plate in a chromatographic chamber, and develop the chromatograms in the Developing solvent system until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, and dry under a stream of nitrogen for about 10 min. Position the dried plate once again in the same chromatographic chamber, and again develop the chromatograms until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, and dry under a current of warm air for about 15 min. Examine the plate under short-wavelength UV light, and compare the intensities of any secondary spots observed in the chromatogram of the Sample solution with those of the principal spots in the chromatograms of the Standard solutions.

Acceptance criteria: The intensity of any secondary spot from the Sample solution is NMT the principal spot from Standard solution A (0.2%), and the sum of the intensities of the secondary spots from the Sample solution corresponds to NMT 1.0%.

5 SPECIFIC TESTS

LOSS ON DRYING (731)

Analysis: Dry a sample under vacuum at room temperature for 6 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, protected from heat and light.

USP REFERENCE STANDARDS (11)

USP Metyrapone RS