Mitoxantrone Hydrochloride

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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C₂₂H₂₈N₄O₆ · 2HCl           517.40

9,10-Anthracenedione, 1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-, dihydrochloride; 1,4-Dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]anthraquinone dihydrochloride

CAS RN: 70476-82-3.

1 DEFINITION

Mitoxantrone Hydrochloride contains NLT 97.0% and NMT 102.0% of mitoxantrone hydrochloride (C₂₂H₂₈N₄O₆ · 2HCl), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy, 197A or 197K _{(CN 1-MAY-2020)}: Meets the requirements

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

PROCEDURE

Solution A: 0.09 g/mL of sodium 1-heptanesulfonate prepared as follows. Dissolve 22.0 g of sodium 1-heptanesulfonate in 150 mL of water. Pass through a filter of NMT 0.5-µm pore size and transfer the filtrate to a 250-mL volumetric flask. Wash the filter with 50 mL of water and add the washings to the flask. Add 32.0 mL of glacial acetic acid to the flask, and dilute with water to volume.

Mobile phase: Acetonitrile, Solution A, and water (10:1:30)

System suitability solution: 0.2 mg/mL of monoalkyl mitoxantrone hydrochloride and 0.1 mg/mL of mitoxantrone hydrochloride from USP Mitoxantrone System Suitability Mixture RS in Mobile phase

Standard solution: 0.4 mg/mL of USP Mitoxantrone Hydrochloride RS prepared as follows. Transfer a suitable amount of USP Mitoxantrone Hydrochloride RS to an appropriate volumetric flask. Add 80% of the flask volume of Mobile phase. Sonicate for about 5 min to dissolve. Cool to room temperature and dilute with Mobile phase to volume.

Sample solution: 0.4 mg/mL of Mitoxantrone Hydrochloride prepared as follows. Transfer a suitable amount of Mitoxantrone Hydrochloride to an appropriate volumetric flask. Add 80% of the flask volume of Mobile phase. Sonicate for about 5 min to dissolve. Cool to room temperature and dilute with Mobile phase to volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

Column: 3.9-mm x 30-cm; 10-µm packing L11

[NOTE-After use, wash the column with a mixture of acetonitrile and water (50:50), and store in this mixture.]

Flow rate: 3 mL/min

Injection volume: 50 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for mitoxantrone and monoalkyl mitoxantrone hydrochloride are about 1.0 and 1.4, respectively.]

Suitability requirements

Resolution: NLT 3.0 between mitoxantrone and monoalkyl mitoxantrone hydrochloride, System suitability solution

Tailing factor: NMT 2.0 for mitoxantrone, System suitability solution

Capacity factor, k': NLT 3.5 for mitoxantrone, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of mitoxantrone dihydrochloride (C₂₂H₂₈N₄O₆ · 2HCl) in the portion of Mitoxantrone Hydrochloride taken:

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

r_u = peak area of mitoxantrone from the Sample solution

r_s = peak area of mitoxantrone from the Standard solution

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

C_u = concentration of Mitoxantrone Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: 97.0%–102.0% on the anhydrous basis

4 IMPURITIES

4.1 ORGANIC IMPURITIES

Analysis: Using the chromatogram of the Sample solution obtained as directed in the Assay, calculate the percentage of each impurity in the portion of Mitoxantrone Hydrochloride taken:

Result = (r_U /r_T ) × 100

r_U = peak response of each impurity

r_T = sum of all peak responses

Acceptance criteria

Individual impurities: NMT 1.0%

Total impurities: NMT 2.0%

4.2 LIMIT OF ALCOHOL

Proceed as directed in Residual Solvents (467).

Acceptance criteria: NMT 1.5%

5 SPECIFIC TESTS

WATER DETERMINATION (921), Method 1: NMT 6.0%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers.

USP REFERENCE STANDARDS (11)

USP Mitoxantrone Hydrochloride RS

USP Mitoxantrone System Suitability Mixture RS

[(2-hydroxyethyl) 0.2 mg of 1-Amino-5,8-dihydroxy-4-((2-[(2-hydroxyethyl)amino]ethyl)amino) anthracene-9,10-dione hydrochloride [monoalkyl mitoxantrone hydrochloride (C₁₈H₁₉N₃O₅ · HCI, 393.82)) and 0.1 mg of USP Mitoxantrone Hydrochloride RS