| Pemetrexed disodium is a novel antifolate antimetabolite with multiple enzyme targets involved in both pyrimidine synthesis and purine synthesis. It has shown encouraging activity in a wide range of tumors, including non-small cell lung carcinoma (NSCLC), malignant mesothelioma, and carcinomas of the breast, colorectum, uterine cervix, head and neck, and bladder.According to material production-techniques and structure characteristic, scientific experiments had been done to establish the quality standard of pemetrexed disodium. The study was emphasized on character, identification, examination, contents determination and stability. Specifically, the research focused on studies of measuring methodologies of related substances, resolution of D-enantiomers from pemetrexed disodium , contents of the drug and the limit of residual solvent.In this paper, HPLC methods were described and developed to quantitatively determine pemetrexed disodium assay and separate the enantiomers of pemetrexed disodium with chiral mobile phase additives. A GC method was established to determinate the residual solvent. Above methods were validated based on the ICH guideline and the results shown the good specificity, accuracy, precision, repeatability and rubstiness.The method was established for determination the related substances and contents of pemetrexed disodium. The mobile phase was 0.05mol/L sodium phosphate(pH3.0)–acetonitril (85:15, v/v) and the wavelength was 227nm. The calibration curve was linear within certain concentration range.The HPLC method which was established for determination of D-enantiomer of pemetrexed disodium used an C18 column withβ-Cyclodextrin as the chiral mobile phase additive, 0.05mol/L ammonium acetate (pH7.0)- acetonitril (95:5, v/v) as mobile phase. Two enantiomers could be separated well with resolution better than 2.0. The limit of residual solvent in pemetrexed disodium drug had been tested, and the drug was qualified.
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