The Impurity Profile Research And Controlling In Methylprednisolone

Methylprednisolone is listed among corticosteroid APIs (active pharmaceuticalingredient). In order to improve the quality of Methylprednisolone and with the ultimatepurpose to assure medication safety of human beings，The research on the impurityprofile of Methylprednisolone and the measurement of quality control forMethylprednisolone is carried out.First of all with reference to analytical method of impurity detection ofMethylprednisolone under Methylprednisolone EP monograph，Some adjustments，which contain the change mobile phase from Acetontrile–water (25:75) toAcetontrile–water (28:72) and the change of gradient elution procedure, are performedto testing parameters. also the accuracy, precision, specificity, limit of detection, limit ofqualification, linearity and range, and robustness of the optimized analytical method arevalidated. And the results indicate that the optimized method can detect the impurity ofMethylprednisolone accurately.Secondarily, ten consecutive batches of Methylprednisolone as well acceleratedstability study on three batches are conducted, thus a general understanding ofimpurities profile of Methylprednisolone produced by above mentioned company areobtained. By this, we are confirmed that six impurities present in Methylprednisolone,among which three impurities produced by manufacturing process are with assay morethan0.10%.Thirdly, by utilizing flash column, TLC and semi-separation HPLC, the threeimpurities are separated and enriched to obtain purity product of the three impuritiesseparately. Through analysis the IR, H-NMR, C-NMR, MS spectra, the three impuritiesare identified as6-Methyl-hydrocortisone,21-dehydromethylprednisolone and11-dehydroxy-Methylprednisolone. Afterwards, the producing mechanism of the threeimpurities is worked out, and it is concluded that three impurities are derived from rawmaterials and intermediates when incomplete synthetic reaction happens.Lastly, on the basis of analytical result of organic impurities in Methylprednisolone,the impurities in Methylprednisolone during the manufacturing process arequantitatively controlled by strengthening quality control on raw materials andintermediates, optimizing parameters of manufacturing process and finally lower theimpurities content in Methylprednisolone and improve Methylprednisolone quality.