Mitotane Tablets

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

Mitotane Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of mitotane (C₁₄H₁₀Cl₄).

2 IDENTIFICATION

A.

Sample: Triturate a quantity from finely powdered Tablets nominally equivalent to 500 mg of mitotane, with 10 mL of water.

Analysis: Pass through a sintered-glass filter funnel, and wash the residue with two 5-mL portions of water. Transfer the residue to a small beaker, add 4 ml of alcohol, heat to boiling, and filter immediately. Allow the filtrate to cool, filter the crystals of mitotane, wash once with 2 mL of alcohol, and dry in vacuum at 60^o for 2 h.

Acceptance criteria: The IR absorption spectrum of a Mineral oil dispersion of the Sample exhibits maxima only at the same wavelengths as that of a similar preparation of USP Mitotane RS.

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B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay _{(RB 1-Aug-2023)}

3 ASSAY

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PROCEDURE

Solution A: Methanol and water (90:10)

Solution B: Methanol

Mobile phase: See Table 1. Return to original conditions, and re-equilibrate the system for 15 min.

Table 1

System suitability solution: 5 mg/mL of USP Mitotane RS and 0.1 mg/mL of USP Mitotane Related Compound A RS in methanol. Use sonication to aid dissolution.

Standard solution: 5 mg/mL of USP Mitotane RS in methanol. Use sonication to aid dissolution.

Sample solution: Nominally 5 mg/mL of mitotane in methanol prepared as follows. Transfer a portion of finely powdered Tablets (NLT 10) into a suitable volumetric flask, dissolve in methanol by sonicating for 1 min and stirring for NLT 10 min. Dilute with methanol to volume. Pass a portion of the solution through a suitable filter of 0.45-µm pore size.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 268 nm

Column: 4.6-mm x 25-cm; 5-µm packing L1

Flow rate: 1 mL/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for mitotane related compound A and mitotane are about 0.95 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 0.85 between mitotane and mitotane related compound A, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of mitotane (C₁₄H₁₀Cl₄) in the portion of Tablets taken:

Result = (r_u /r_s ) × (C_s /C_u ) × 100

r_u = peak response of mitotane from the Sample solution

r_s = peak response of mitotane from the Standard solution

C_s = concentration of USP Mitotane RS in the Standard solution (mg/mL)

C_u = nominal concentration of mitotane in the Sample solution (mg/mL)

_{(RB 1-Aug-2023)}

Acceptance criteria: 90.0%–110.0%

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4 IMPURITIES

PERFORMANCE TESTS

DISINTEGRATION (701)

Time: 15 min, the use of disks being omitted

Acceptance criteria: Meet the requirements

UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

5 ADDITIONAL REQUIREMENTS

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PACKAGING AND STORAGE: Preserve in tight, light-resistance containers. Store at controlled room temperature

_{(RB 1-Aug-2023)}

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USP REFERENCE STANDARDS (11)

USP Mitotane RS

USP Mitotane Related Compound A RS

2,2-Bis(4-chlorophenyl)-1,1-dichloroethane.

C₁₄H₁₀Cl₄        320.04 _{(RB 1-Aug-2023)}