Doxorubicin Hydrochloride 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 Injection is a sterile solution of Doxorubicin Hydrochloride in Sterile Water for Injection made isoosmotic with Sodium Chloride, Dextrose, or other suitable added substances. It contains NLT 90.0% and NMT 115.0% of the labeled amount of doxorubicin hydrochloride (C₁₇H₂₉NO₁₁ · HCI)

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

[NOTE-Protect solutions containing doxorubicin from light.]

Solution A: 0.1% trifluoroacetic acid TS

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

Mobile phase: See Table 1.

Diluent: Solution A and Solution 8 (50:50)

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 Injection

Chromatographic system

(See Chromatography (621), System Suitability)

Mode: LC

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

Column: 2.1mm * 10 - cm; 1.7-um packing 11

Temperatures

Autosampler: 4°

Column: 35°

Flow rate: 0.5 mL/min

Injection volume: 2 pl.

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

Tailing factor: 0.8-1.5, Standard solution

Relative standard deviation: NMT07, San

Analysis

Sample avion and Sampletion

Calculate the percentage of the labelled amount of doxorubicin hydrochloride (CHNO, HCI) in the portion of 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

Acoeptance criteria 90.0%-115.0%

4 IMPURITIES

Change to read:

• Organic Impurities

[Note—Protect solutions containing doxorubicin from light.]

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

Standard solution: 0.008 mg/mL each of USP Doxorubicin Hydrochloride RS and 0.012 mg/mL of USP Doxorubicinone RS in Diluent. [Note—It may be necessary to rst dissolve in acetonitrile, using NMT 5% of the nal volume, before diluting with Diluent.]

Sample solution: Nominally 0.4 mg/mL of doxorubicin hydrochloride in Diluent from Injection

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

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

Relative standard deviation: NMT 5.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of doxorubicinone in the portion of 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 any individual unspecied degradation product in the portion of 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

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.

^d The acceptance criteria of this impurity, if present, would fall under the acceptance criteria for "any other individual degradation product and is included in the total impurities.

5 SPECIFIC TESTS

pH 〈791〉: 2.5–4.5

Sterility Tests 〈71〉, Test for Sterility of the Product to Be Examined, Membrane Filtration: It meets the requirements when tested as directed, the entire contents of all the containers being collected aseptically.

Bacterial Endotoxins Test 〈85〉

Sample solution: 1.1 mg/mL of doxorubicin hydrochloride prepared from Injection in Sterile Water for Injection

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

Other Requirements: It meets the requirements in Injections and Implanted Drug Products 〈1〉.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose or multiple-dose containers, preferably of Type I glass, protected from light. Store in a refrigerator. Injection may be packaged in multiple-dose containers not exceeding 100 mL in volume.