Action and use
Cytotoxic alkylating agent.
Definition
Melphalan Tablets contain Melphalan. They are coated.
The tablets comply with the requirements stated under Tablets and with the following requirements.
Content of melphalan, C13H18Cl2N2O2
90.0 to 110.0% of the stated amount.
Identification
A. Extract a quantity of the powdered tablets containing 25 mg of Melphalan with 50 mL of hot
methanol, filter and dilute 5 mL of the filtrate to 500 mL with
methanol. The
light absorption of the resulting solution,
Appendix II B, exhibits a maximum at 260 nm and a less well-defined maximum at 301 nm.
B. To the remainder of the filtrate obtained in test A add 1 mL of a 5% w/v solution of
4-(4-nitrobenzyl)pyridine in
acetone and evaporate to dryness. Dissolve the residue in 1 mL of hot
methanol and add 0.1 mL of 13.5
m ammonia. A red colour is produced.
Tests
Dissolution
Comply with the requirements for Monographs of the British Pharmacopoeia in the dissolution test for tablets and capsules, Appendix XII B1.
test conditions
(a) Use Apparatus 1, rotating the basket at 100 revolutions per minute.
procedure
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(1) After 45 minutes withdraw a sample of the medium and filter. Use the filtered medium, diluted with
0.1m hydrochloric acid if necessary, expected to contain about 0.0002% w/v of Melphalan.
chromatographic conditions
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 254 nm.
(f) Inject 100 µL of each solution.
mobile phase
2.7 volumes of glacial acetic acid, 180 volumes of methanol and 200 volumes of a 0.375% w/v solution of ammonium carbonate.
determination of content
Calculate the content of melphalan, C13H18Cl2N2O2 in the medium using the declared content of C13H18Cl2N2O2 in melphalan BPCRS.
Uniformity of content
Tablets containing less than 2 mg and/or less than 2% w/w of Melphalan comply with the requirements stated under Tablets using the following method of analysis.
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(2) Add 20 mL of a mixture of 4 volumes of
acetonitrile and 1 volume of
0.1m hydrochloric acid to one tablet, mix with the aid of ultrasound for 10 minutes or until the tablet has disintegrated, filter, discarding the first 5 mL of filtrate, and use the filtrate.
chromatographic conditions
(b) Use isocratic elution and the mobile phase described below.
(c) Use a flow rate of 2 mL per minute.
(d) Use an ambient column temperature.
(e) Use a detection wavelength of 254 nm.
(f) Inject 20 µL of each solution.
mobile phase
2.7 volumes of glacial acetic acid, 180 volumes of methanol and 200 volumes of a 0.375% w/v solution of ammonium carbonate.
determination of content
Calculate the content of C13H18Cl2N2O2 in each tablet using the declared content of C13H18Cl2N2O2 in melphalan BPCRS.
Assay
For tablets containing less than 2 mg and/or less than 2% w/w of Melphalan
Use the average of the 10 individual results determined in the test for Uniformity of content.
For tablets containing 2 mg or more and 2% w/w or more of Melphalan
Carry out the method for liquid chromatography, Appendix III D, using the following solutions.
(2) Add about 300 mL of a mixture of 4 volumes of
acetonitrile and 1 volume of
0.1m hydrochloric acid to 10 tablets, shake until the tablets have disintegrated (about 30 minutes), mix with the aid of ultrasound for 5 minutes, dilute to 500 mL with the same solvent mixture, filter, discarding the first 20 mL of filtrate, and use the filtrate.
chromatographic conditions
The chromatographic conditions described under Uniformity of content may be used.
determination of content
Calculate the content of C13H18Cl2N2O2 in the tablets using the declared content of C13H18Cl2N2O2 in melphalan BPCRS.