भारतीय भेषज संहिता आयोग
Epirubicin Hydrochloride (30-01-2018)
Epirubicin Hydrochloride
C27H30ClNO11 Mol. Wt. 580.0
Epirubicin hydrochloride is (8S,10S)-10-[(3-Amino-2,3,6-trideoxy-α-L-arabino-hexopyranosyl)oxy]-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione hydrochloride.
Epirubicin hydrochloride contains not less than 97.0 per cent and not more than 102.0 per cent of C27H30ClNO11, calculated on the anhydrous basis.
Category.Anticancer.
Dose.120 to 135 mg per day.
Description.An orange-red powder.
Identification
- Determine by infrared absorption spectrophotometry (2.4.6). Compare the spectrum with that obtained withepirubicin hydrochloride RSor with the reference spectrumof epirubicin hydrochloride.
- In the Assay, the principal peak in the chromatogram obtained with the test solution corresponds to the peak in the chromatogram obtained with the reference solution (a).
- Dissolve about 10 mg in 0.5 ml ofnitric acid, add 0.5 ml of water and heat over a flame for 2 min. Allow to cool and add 0.5 ml of silver nitrate solution. A white precipitate is formed.
Tests
pH(2.4.24). 4.0 to 5.5, determined in 0.5 per cent w/v solution in carbon dioxide-free water.
Related substances. Determine by liquid chromatography (2.4.14).
Test solution. Dissolve 25.0 mg of the substance under examination in the mobile phase and dilute to 25.0 ml with the mobile phase.
Reference solution (a).A 0.1 per cent w/v solution of epirubicin hydrochloride RS in the mobile phase.
Reference solution (b). Dissolve 10 mg of epirubicin hydrochloride RS and 10 mg of doxorubicin hydrochloride RS in the mobile phase and dilute to 100 ml with the mobile phase.
Reference solution (c). Dissolve 10 mg of doxorubicin hydrochloride RS in a mixture of 5 ml of water and 5 ml of orthophosphoric acid. Allow to stand for 30 min. Adjust to pH 2.6 with an 8 per cent w/v solution of sodium hydroxide. Add 15 ml of acetonitrile, 10 ml of methanol and mix.
Reference solution (d). Dilute 1.0 ml of the test solution to 100.0 ml with the mobile phase.
Chromatographic system
– a stainless steel column 25 cm × 4.6 mm, packed with trimethylsilane bonded to porous silica (5 µm),
– column temperature: 35°,
– mobile phase: a mixture of 54 volumes of a buffer solution prepared by dissolving 3.7 g of sodium lauryl sulphate and 28 ml of dilute phosphoric acid in 1000 ml ofwater, 17 volumes of methanol and 29 volumes of acetonitrile,
– flow rate: 2.5 ml per minute,
– spectrophotometer set at 254 nm,
– injection volume: 10 µl.
Name Relative Correction
retention time factor
Epirubicin impurity A1 0.3 0.7
Epirubicin impurity B2 0.4 ---
Epirubicin impurity C3 0.8 ---
Epirubicin (Retention time:
about 9.5 minutes) 1.0 ---
Epirubicin impurity D4 1.5 ---
Epirubicin impurity E5 1.1 ---
Epirubicin impurity F6 1.7 ---
Epirubicin impurity G7 2.1 ---
1R = OH: (8S,10S)-6,8,10,11-tetrahydroxy-8-(hydroxyacetyl)-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione (doxorubicin one),
2R = H: (8 B.S,10S)-8-acetyl-6,8,10,11-tetrahydroxy-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione (daunorubicin one),
3(8S,10S)-10-[(3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy]-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione (doxorubicin),
4(8S,10S)-8-acetyl-10-[(3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy]-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione (daunorubicin),
5(8S,10S)-10-[(3-amino-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)oxy]-6,8,11-trihydroxy-8-[(1RS)-1-hydroxyethyl]-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione (dihydrodaunorubicin),
6(8S,10S)-8-acetyl-10-[(3-amino-2,3,6-trideoxy-α-L-arabino-hexopyranosyl)oxy]-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione (epi-daunorubicin),
78,8′-[(2R,4R)-4-hydroxy-2-(hydroxymethyl)-1,3-dioxolan-2,4-diyl]bis[(8S,10S)-10-[(3-amino-2,3,6-trideoxy-α-L-arabino-hexopyranosyl)oxy]-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione] (epirubicin dimmer).
Inject reference solutions (b), (c), (d) and the test solution.
Run the chromatogram time 3.5 times the retention time of epirubicin.
Identification of impurities. Use the 2nd most abundant peak present in the chromatogram obtained with reference solution (c) to identify impurity A.
Inject the reference solution (b). The test is not valid unless the resolution between the peaks corresponding to impurity C and epirubicin is not less than 2.0.
Inject reference solution (d) and the test solution. In the chromatogram obtained with the test solution, the area of peak corresponding to epirubicin impurities A and C is not more than the area of the principal peak in the chromatogram obtained with reference solution (d) (1.0 per cent). The area of any secondary peak is not more than 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (d) (0.5 per cent). The sum of areas of all the secondary peaks is not more than 2 times the area of the principal peak in the chromatogram obtained with reference solution (d) (2.0 per cent). Ignore any peak with an area less than 0.05 times the area of the principal peak in the chromatogram obtained with reference solution (d) (0.05 per cent).
Acetone (5.4). Not more than 1.5 per cent.
Water (2.3.43).Not more than 4.0 per cent, determined on 0.1 g.
Bacterial endotoxins (2.2.3). Not more than 1.1 Endotoxin Unit per mg of epirubicin hydrochloride, if intended for use in the manufacture of parenteral preparation without a further appropriate procedure for the removal of bacterial endotoxins.
Assay. Determine by liquid chromatography (2.4.14).as described under related substances with the following modification.
Inject reference solution (a) and the test solution.
Calculate the content of C27H30ClNO11.
Storage.In an airtight container, protected from light, at a temperature of 2° to 8°. If the substance is sterile, store in a sterile, airtight, tamper-proof container.
Solubility
Soluble in water and in methanol, slightly soluble in anhydrous ethanol, practically insoluble in acetone.
