Epirubicin Hydrochloride
C27H29NO11·HCl 579.98
5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-
-l-arabino-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)-;
(1S,3S)-3-Glycoloyl-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1-naphthacenyl-3-amino-2,3,6-trideoxy--l-arabino-hexopyranoside hydrochloride.
[56390-09-1].
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C27H29NO11·HCl 579.98
5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-
-l-arabino-hexopyranosyl)oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)-;
(1S,3S)-3-Glycoloyl-1,2,3,4,6,11-hexahydro-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1-naphthacenyl-3-amino-2,3,6-trideoxy-
-l-arabino-hexopyranoside hydrochloride.
[56390-09-1].DEFINITION
Epirubicin Hydrochloride contains NLT 97.0% and NMT 102.0% of C27H29NO11·HCl, calculated on the anhydrous and solvent-free basis.
IDENTIFICATION
• B.
The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
• C. Identification Tests—General, Chloride 
191
:
A 10 mg/mL solution in a mixture of nitric acid and water (1:1) meets the requirements.
191:
A 10 mg/mL solution in a mixture of nitric acid and water (1:1) meets the requirements.
ASSAY
• Procedure
[Note—Allow the System suitability solution, Standard solution, and the Sample solution to stand for 3 h before use. ]
Solution A:
Dissolve 3.7 g of sodium lauryl sulfate in 950 mL of water. To the resulting solution, add 28 mL of 10% phosphoric acid, and dilute with water to 1000 mL.
Mobile phase:
Acetonitrile, methanol, and Solution A (29:17:54)
System suitability solution:
0.1 mg/mL each of USP Epirubicin Hydrochloride RS and USP Doxorubicin Hydrochloride RS in Mobile phase
Standard solution:
1 mg/mL of USP Epirubicin Hydrochloride RS in Mobile phase
Sample solution:
1 mg/mL of Epirubicin Hydrochloride in Mobile phase
Chromatographic system
Mode:
LC
Detector:
UV 254 nm
Column:
4.6-mm × 25-cm; 6-µm packing L13
Temperature:
35
Flow rate:
2.5 mL/min
Injection size:
10 µL
Run time:
About 3.5 times the retention time of the epirubicin peak
System suitability
Sample:
System suitability solution
Suitability requirements
Resolution:
NLT 2.0 between doxorubicin and epirubicin
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of C27H29NO11·HCl in the portion of Epirubicin Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × 100
| rU | = | = peak response from the Sample solution |
| rS | = | = peak response from the Standard solution |
| CS | = | = concentration of the Standard solution (mg/mL) |
| CU | = | = concentration of the Sample solution (mg/mL) |
Acceptance criteria:
97.0%–102.0% on the anhydrous and solvent-free basis
IMPURITIES
Organic Impurities
• Procedure 1
[Note—Allow the System suitability solution, Sample solution, and Standard solution to stand for 3 h before use. ]
Mobile phase, System suitability solution, Sample solution, Chromatographic system, and System suitability:
Proceed as directed in the Assay.
Standard solution:
0.01 mg/mL of USP Epirubicin Hydrochloride RS in Mobile phase
Peak identification solution:
Dissolve 10 mg of USP Doxorubicin Hydrochloride RS in 10 mL of a mixture of water and phosphoric acid (1:1). Allow to stand for 30 min. Adjust with 2 N sodium hydroxide solution to a pH of 2.6. Add 15 mL of acetonitrile and 10 mL of methanol, and mix.
Analysis
Samples:
Sample solution, Standard solution, and Peak identification solution
[Note—Use the Peak identification solution to identify peaks using the relative retention times in Impurity Table 1. ]
Calculate the percentage of each impurity in the portion of Epirubicin Hydrochloride taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
| rU | = | = peak response of the impurity peak from the Sample solution |
| rS | = | = peak response of the epirubicin peak from the Standard solution |
| CS | = | = concentration of USP Epirubicin Hydrochloride RS in the Standard solution (mg/mL) |
| CU | = | = concentration of Epirubicin Hydrochloride in the Sample solution (mg/mL) |
| F | = | = relative response factor (see Impurity Table 1) |
Acceptance criteria
Individual impurities:
See Impurity Table 1.
Total impurities:
NMT 3.0%
Impurity Table 1
| Name | Relative Retention Time |
Relative Response Factor |
Acceptance Criteria, NMT (%) |
|---|---|---|---|
| Doxorubicinone | 0.3 | 1.4 | 1.0 |
| Daunorubicinone | 0.4 | 1.0 | 0.5 |
| Doxorubicin | 0.8 | 1.0 | 1.0 |
| Epirubicin | 1.0 | — | — |
| Dihydrodaunorubicin | 1.1 | 1.0 | 0.5 |
| Daunorubicin | 1.5 | 1.0 | 0.5 |
| Epidaunorubicin | 1.7 | 1.0 | 1.0 |
| Epirubicin dimer | 2.1 | 1.0 | 1.0 |
| Individual unspecified impurity | — | 1.0 | 0.5 |
SPECIFIC TESTS
• Water Determination, Method Ic 921:
NMT 4.0%
921:
NMT 4.0%
• pH 791:
4.0–5.5 for a 5 mg/mL solution
791:
4.0–5.5 for a 5 mg/mL solution
• Bacterial Endotoxins Test 85:
NMT 1.1 USP Endotoxin Units/mg, where the label states that Epirubicin Hydrochloride is sterile or must be subjected to further processing during the preparation of injectable dosage forms.
85:
NMT 1.1 USP Endotoxin Units/mg, where the label states that Epirubicin Hydrochloride is sterile or must be subjected to further processing during the preparation of injectable dosage forms.
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Store in airtight containers, protected from light, at a temperature between 2 and 8. If the substance is sterile, store in a sterile, airtight, tamper-proof container.
and 8. If the substance is sterile, store in a sterile, airtight, tamper-proof container.
• Labeling:
Where applicable, the label states that the substance is free from bacterial endotoxins.
• USP Reference Standards 11
11
USP Endotoxin RS
USP Doxorubicin Hydrochloride RS 
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USP Epirubicin Hydrochloride RS
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Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Ahalya Wise, M.S.
Senior Scientific Liaison 1-301-816-8161 |
(SM12010) Monographs - Small Molecules 1 |
| 85 |
Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison 1-301-816-8339 |
(GCM2010) General Chapters - Microbiology |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
USP35–NF30 Page 3058
Pharmacopeial Forum: Volume No. 35(2) Page 274