Hplc-uv method development and impurity profiling of the marine anticancer agent aplidine in raw drug substance and pharmaceutical dosage form

摘要

The development and validation of a reversed-phase high performance liquid chromatorgaphic(RP-HPLC)method with ultraviolet(UV) detection for the quantification and purity determination of aplidine in raw drug substance nd pharmaceutical dosage form in described.Using this method,the aplidine rotamers present as a consequence of cis-trans isomerism of the peptide bond between the proline and pyruvoyl moieties in the molecule,elute as one single peak.Linear calibration curves in the range of 12.5-300 #mu#g/ml of aplidine with correlation coefficients >0.999 were obtained.Within-run and between-run precisions were <=2.2 percent and accuracy was within 100.6-101.4 percent.A profile of recurrent impurities was drawn up from several lots of aplidine raw durg substance manufactured thus far.Major impurities were identified as didemnin-A,acetyldidemnin A and noraplidine using liquid chromatography-mass spectrometry(LC-MS).No significant differences in chromatographic profile between aplidine raw drug substance and its pharmaceutical dosage form were found.