足叶乙甙同质异晶的研究

STUDY OF THE POLYMORPH OF ETOPOSIDUM

用二种不同工艺制得的足叶乙甙具有不同的差热图谱,测熔点时熔融过程不一,经用粉末X-光衍射检查,确认二种工艺所得产品具有不同晶型,其原因是精制时使用了不同的溶剂。变换溶剂可使二种晶型彼此转变。晶型B测定熔点升温到190℃左右时,出现类似潮解的湿润状态,这是转晶过程的开始,由B型转变成A型。晶型A较之晶型B处于较低能态,应具有较好的稳定性。足叶乙甙的制剂为溶液态,晶型的差异与药效无关。

Etoposidum:4′-demethyl-epipodophyllotoxin-β-D-ethylidene-pyrano-glucoside orVP-16-213 in trade name is a semisynthetic antineoplastic drug. We found that it has two differentkinds of crystal form named crystal A and B, they were crystallized from methanol and ethanol respec-tively. Their structures were identified by NMR and MS. They have similar infrared spectrum butwith repeatable small differences. The powder X-ray diffraction pattern of the two kinds of crystalsare quite different. The DSC curve of crystal A is rather smooth but that of crystal B shows abnormalpositive and negative peaks. On the other hand, they have the same kind of smooth TGA curves. Thisfact shows that the positive and negative peaks are not the result of chemical reaction. After heatingcrystal B in DSC oven at 190°C and 250°C ,respectively,their IR spectra showed that the pattern ofthe first one did not change, but the second one changed to the spectrum of crystal A. This reveals thatthe positive peak is due to the melting of crystal B and the negative peak is the result of the formationof crystal A. The pharmaceutic preparation of VP-16-213 is its glycerine solution, so the crystal formdoes not influence the efficacy of the drug.