Doxorubicin Hydrochloride for 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

Doxorubicin Hydrochloride for Injection is a sterile mixture of Doxorubicin Hydrochloride and Lactose, It contains NLT 90.0% and NMT 115.0% of the labeled amount of doxorubicin hydrochloride(C₁₇H₂₉NO₁₁ · HCI).

[CAUTION-Great care should be taken to prevent inhaling particles of Doxorubicin Hydrochloride and exposing the skin to it.]

2 IDENTIFICATION

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

B. The UV spectrum of the doxorubicin peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Change to read:

PROCEDURE

Solution A: 0.1% Trifluoroacetic acid prepared by diluting 1.0 mL of trifluoroacetic acid with water to 1 L

Solution B: Acetonitrile, methanol, and trifluoroacetic acid (800:200:1)

Mobile phase: See Table 1.

Diluent: Solution A and Solution B (50:50)

[Nore-Protect solutions containing doxorubicin from light.]

System suitability solution: 0.1 mg/ml, each of USP Doxorubicin Hydrochloride RS and USP Epirubicin Hydrochloride RS in Diluent

Standard solution: 0.1 mg/ml. of USP Doxorubicin Hydrochloride RS in Diluent

Sample solution: Nominally 0.1 mg/mL of doxorubicin hydrochloride in Diluent from Doxorubicin Hydrochloride for Injection prepared as follows. Add 5 mL of Diluent into the container of Doxorubicin Hydrochloride for Injection, and transfer the contents to a volumetric flask of appropriate size. Rinse the container with additional Diluent NLT 3 times. Dilute with Diluent to volume, and mix.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm. For Identification test 8, use a photo-diode array detector in the range of 190-400 nm.

Column: 0.1 - mm * 10 - c ; 1.7-µm packing L1

Temperatures

Autosampler: 4"

Column: 35 deg

Flow rate: 0.5 mL/min

Injection volume: 2 ul

System suitability

Samples: System suitability solution and Standard solution

[NOTE-The relative retention times for doxorubicin and epirubicin are 1.0 and 1.05, respectively.]

Suitability requirements

Resolution: NLT 1.5 between doxorubicin and epirubicin, System suitability solution

Tailing factor: 0.8–1.5, Standard solution

Relative standard deviation: NMT 0.73%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of doxorubicin hydrochloride (C H NO · HCl) in the portion of Doxorubicin

Hydrochloride for Injection taken:

Result = (r_U/(r_S) × (C_S /C_U) × P x F x 100

r_U = peak response of doxorubim from the Sample solution

r_S = peak response of dovorubicin from the Standard solution

C_S = concentration of US Doxorubicin Heskochlaride RS, in the Stardard solution (mg/ml)

C_U = nominal concentration of dusarubron hydrochloride in the Sample sulation (mg/ml)

P = potency of doxorubicin hydrochloride in USP Doxorubicin Hydrochloride RS (µg/mg)

F = conversion factor 0.001 mg/μg

Acceptance criteria: 90.0%–115.0%

4 IMPURITIES

Change to read:

ORGANIC IMPURITIES

Mobile phase, Diluent, System suitability solution, and Chromatographic system: Proceed as directed in the Assay.

Nore-Protect solutions containing doxorubicin from light.]

Standard solution: 0.002 mg/ml., each of USP Doxorubicin Hydrochloride RS, USP Doxorubicinone RS, and USP Daunorubicinone RS in Diluent

Sample solution: Nominally 0.4 mg/mL of doxorubicin hydrochloride in Diluent from Doxorubicin Hydrochloride for Injection prepared as follows. Add 5 mL of Diluent into the container of Doxorubicin Hydrochloride for Injection, and transfer the contents to a volumetric flask of appropriate size. Rinse the container with additional Diluent NLT 3 times. Dilute with Diluent to volume, and mix.

System suitability

Samples: System suitability solution and Standard solution [NOTE-See Table 2 for the relative retention times.)

Suitability requirements

Resolution: NLT 1.5 between doxorubicin and epirubicin, System suitability solution

Relative standard standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of doxorubicinone in the portion of Doxorubicin Hydrochloride for Injection taken:

Result = (r_U/(r_S) × (C_S /C_U) × P x 100

r_U = peak response of doxorubicinone from the Sample solution

r_S = peak response of doxorubicinone from the Standard solution

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

C_U = nominal concentration of doxorubicin hydrochloride in the Sample solution (mg/mL)

P = potency of doxorubicinone in USP Doxorubicinone RS (mg/mg)

Calculate the percentage of daunorubicinone in the portion of Doxorubicin Hydrochloride for Injection taken:

Result = (r_U/(r_S) × (C_S /C_U) × P x 100

r_U = peak response of daunorubicinone from the Sample solution

r_S = peak response of daunorubicinone from the Standard solution

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

C_U = nominal concentration of doxorubicin hydrochloride in the Sample solution (mg/mL)

P = potency of daunorubicinone in USP Doxorubicinone RS (mg/mg)

Calculate the percentage of any individual unspecied degradation product in the portion of Doxorubicin Hydrochloride for Injection taken:

Result = (r_U/(r_S) × (C_S /C_U) × P × F × 100

r_U = peak response of each degradation product from the Sample solution

r_S= peak response of doxorubicin from the Standard solution

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

C_U = nominal concentration of doxorubicin hydrochloride in the Sample solution (mg/mL)

P = potency of doxorubicin in USP Doxorubicin Hydrochloride RS (µg/mg)

F = conversion factor, 0.001 mg/µg

in USP Doxorubicin Hydrochloride RS (µg/mg)

F = conversion factor, 0.001 mg/µg

Acceptance criteria: See Table 2.

^a For resolution measurement only. Not to be reported; not to be included in total impurities.

^b (8S,10S)-6,8,10,11-Tetrahydroxy-8-(hydroxyacetyl)-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione.

^c (8S,10S)-8-Acetyl-6,8,10,11-tetrahydroxy-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione.

5 SPECIFIC TESTS

CONSTITUTED SOLUTION: At the time of use, it meets the requirements in injections and implanted Drug Products (1): Specific Tests. Completeness and clarity of solutions.

STERILITY TESTS (71): It meets the requirements when tested as directed in Test for Sterility of the Product to Be Examined. Membrane Filtration.

the entire contents of all the containers being collected aseptically with the aid of 200 ml of Fluid A before filtering.

WATER DETERMINATION, Method (921)

Sample solution: Prepare as directed for a hygroscopic specimen.

Acceptance criteria: NMT 4.0%

pH (791)

Sample solution: Constitute as directed in the labeling using water as the diluent.

Acceptance criteria: 4.5-6.5

BACTERIAL ENDOTOXINS TENT (85)

Sample solution: 1.1 mg/mL of doxorubicin hydrochloride from Doxorubicin Hydrochloride for Injection

Acceptance criteria: NMT 2.2 USP Endotoxin Units/mg of doxorubicin hydrochloride

UNIFORMITY OF DOSABE UNITS (905); Meets the requirements

LABELING (7), LABELS AND LABELING FOR INJECTABLE PRODUCTS: Meets the requirements.

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve as described in Packaging and Storage Requirements (659). Injection Packaging. Packaging for constitution.

except that multiple-dose containers may provide for the withdrawal of NMT 100 ml when constituted as directed in the labeling. Store unreconstituted vials at controlled room temperature. Protect from light.