Mitoxantrone Injection

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

Mitoxantrone Injection is a sterile solution of Mitoxantrone Hydrochloride in Water for Injection. It contains the equivalent of NLT 90.0% and NMT 105.0% of the labeled amount of mitoxantrone  (C₂₂H₂₈N₄O₆).

2 IDENTIFICATION

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A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Ultraviolet-Visible Spectroscopy: 1970 _{(CN 1-MAY-2020) (USP 1-MAY-2019)}

Standard solution: 0.01 mg/mL of USP Mitoxantrone Hydrochloride RS (equivalent to 0.01 mg/mL of mitoxantrone) prepared as follows.

Transfer a suitable amount of USP Mitoxantrone Hydrochloride RS to an appropriate volumetric flask. Add 50% of the flask volume of water and 10% of the flask volume of 1 N hydrochloric acid VS. Dilute with water to volume.

Sample solution: Nominally 0.01 mg/mL of mitoxantrone from Injection prepared as follows. Transfer a volume of Injection equivalent to 2 mg of mitoxantrone to a 200-ml volumetric flask containing about 50% of the flask volume of water and 10% of the flask volume of 1 N hydrochloric acid VS. Dilute with water to volume.

Acceptance criteria: Meets the requirements _{(USP 1-May-2019)}

Add the following:

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay _{(USP 1-May-2019)}

3 ASSAY

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PROCEDURE

Solution A: 0.09 mg/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 (USP 1-May-2019) 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) _{(USP 1-May-2019)}

System suitability solution: 0.2 mg/mL of monoalkyl mitoxantrone hydrochloride (USP 1-May-2019) and 0.1 mg/mL of mitoxantrone hydrochloride from USP Mitoxantrone System Suitability Mixture RS in Mobile phase

Standard solution: 0.46 mg/mL of USP Mitoxantrone Hydrochloride RS (equivalent to 0.4 mg/mL of mitoxantrone) 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: Nominally 0.4 mg/mL of mitoxantrone from Injection, in Mobile phase

Chromatographic system

Chromatography (621), System Suitability

Mode: LC

Detector: UV 254 nm.

Column: 3.9 mm x 30 cm; 10-µm (USP 1-May-2019) 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 _{(USP 1-May-2019)} are about 1.0 and 1.4.

_{(USP 1-May-2019)} respectively.

Suitability requirements

Resolution: NLT 3.0 between mitoxantrone and monoalkyl mitoxantrone hydrochloride _{(USP 1-May-2019)} 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 1.0%, _{(USP 1-May-2019)} Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of mitoxantrone (C₂₂H₂₈N₄O₆) in the portion of Injection taken:

Result = (r_u /r_s ) × (C_s /C_u ) × (M_r1 /M_r2 ) × 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 = nominal concentration of mitoxantrone in the Sample solution (mg/mL)

M_r1 = molecular weight of mitoxantrone, 444.49

M_r2 = molecular weight of mitoxantrone hydrochloride, 517.40

Acceptance criteria: 90.0%–105.0%

4 IMPURITIES

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 Injection taken:

Result = (r_u/r_T) x 100

r_u= peak response of each impurity

r_T= sum of all peak responses

Acceptance criteria

Individual impurities: NMT 1.5%

Total impurities: NMT 3.0%

5 SPECIFIC TESTS

PH (791): 3.0-4.5

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BACTERIAL ENDOTOXINS TEST (85): Meets the requirements _{(USP 1-May-2019)}

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STERILITY TESTS (71): Meets the requirements

OTHER REQUIREMENTS: It meets the requirements under Injections and Implanted Drug Products (1).

6 ADDITIONAL REQUIREMENTS

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PACKAGING AND STORAGE: Preserve in single dose or multiple-dose containers, preferably of Type I glass. Do not freeze. Store at controlled room temperature. _{(USP 1-May-2019)}

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LABELING: Label Injection to state both the content of the active moiety and the name of the salt used in formulating the article. Label Injection. to indicate that it is to be diluted to appropriate volume with _{(USP 1-May-2019)} Suitable fluid before administration.

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USP REFERENCE STANDARDS (11)

USP Mitoxantrone Hydrochloride RS

USP Mitoxantrone System Suitability Mixture RS

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 · HCl, 393.82)] and 0.1 mg of USP Mitoxantrone Hydrochloride RS _{(USP 1-May-2019)}