Study On The Separation And Enrichment Of Paclitaxel By Simulated Moving Bed

Separating and enriching paclitaxel from raw material with a simulated moving bed(SMB)was investigated in this paper.By introducing solvent gradient,the eluotropic strength of the liquid in zone Ⅱ is higher than that in zone Ⅲ,thus paclitaxel can move forward in zone Ⅱ but backward in zone III to be selectively trapped in SMB consequently under suitable operating conditions.Meanwhile,the impurities run out of SMB continuously and thus paclitaxel was separated from the impurities.The whole separation process consists of two steps of purification.In the first step,methanol-water was used as the mobile phase.The influences of feeding rate,feeding cycle,liquid flow rate and liquid composition in every zone,switching interval and column configuration were studied in detail.It was found that the retention of paclitaxel increased with the removal of impurities,and hence the flow rate and switching interval should be adjusted correspondingly to effectively trap paclitaxel.Cephalomannanine with a certain purity could be collected while qualified paclitaxel could not be obtained due to an unknown impurity.The retension of the impurity is slightly stronger than that of paclitaxel in the mobile phase of methanol-water.Thereby the impurity is very difficult to be removed due to the tag-along effect.However,the impurity is a less retained solute,in comparision with paclitaxel in the mobile phase of acetonitrile-water and thus it would be easily removed due to the displacement effect.In the second step,acetonitrile-water was used as the mobile phase.The effects of flow rate and amount of water were studied.The results showed that the impurity and paclitaxel could be effectively separated:paclitaxel was mainly distributed in columns 3-6 while the impurity distributed in columns 7-8.The solute out of columns 1-6 were qualified and collected.The optimum conditions were obtained:in the first purification,methanol-water was used as the mobile phase,and 7-epi-10-deacetyl paclitaxel and the majority of impurities were removed,and the side-product cephalomannine with a yield of 93%and a purity of 98%was obtained.In the second purification,acetonitrile-water was used,to remove the unknown impurity.The results showed that it took 16.22 h to process 13.4 g raw material using eight 1cm×10 cm columns packed with 10-20 μm reverse phase C18 silica gel,giving paclitaxel with a purity of 99.8%and a yield of 91.4%.