TACROLIMUS AND ASCOMYCIN

Process for purifying Tacrolimus - Patent Application 20080000834 The invention provides a process for the chromatographic purification of Tacrolimus, using a silver modified sorbent, selected from the group consisting of silver modified aluminum oxide, zirconium oxide, styrene divinylbenzene copolymer, adsorption resin, cation exchange resin, anion exchange resin, reverse phase silica gel, and cyano silica-gel, and separating the Tacrolimus chromatographically with the silver modified sorbent as a stationary phase. 1. A process for separating Tacrolimus from impurities comprising: a) loading a mixture comprised of tacrolimus and impurities in a bed of sorbent pretreated with silver ions, wherein the sorbent is selected from the group consisting of silver modified aluminum oxide, zirconium oxide, styrene divinylbenzene copolymer, adsorption resin, cation exchange resin, anion exchange resin, reverse phase silica gel, and cyano silica-gel; and b) eluting the mixture from the bed of sorbent resin to separate Tacrilomus from impurities present in the mixture. Preferably, the eluted fractions are recovered by collecting groups of fractions, and evaporating the solvent, thus, providing a sample. The recovered sample is then analyzed, preferably, by HPLC, providing the content of Tacrolimus, Ascomycin, and Dihydrotacrolimus in the sample. Typically, as the elution process progresses, the level of Ascomycin and Dihydrotacrolimus decreases while the level of Tacrolimus increases. Preferably, the process is repeated, so that the final sample contains substantially pure Tacrolimus. Preferably, the final sample contains at least about 93 percent area by HPLC of Tacrolimus, more preferably, at least about 95 percent area by HPLC of Tacrolimus, and, even more preferably, at least about 99 percent area by HPLC. Preferably, the final sample also contains less than about 0.20 percent area by HPLC of Ascomycin, more preferably, less than about 0.