双磷酸盐类药物精制工艺

为避免使用醇类溶剂精制双磷酸盐类药物易导致的基因毒性风险和溶剂化合物问题，探讨双磷酸盐类药物的非醇类溶剂精制工艺．采用非醇类溶剂（丙酮和甲基异丁酮）分别对伊班膦酸钠和帕米磷酸钠进行精制，通过滴定法、气相色谱法（GC）等手段测定了精制前后亚磷酸盐含量及产物的残留溶剂．结果表明，采用丙酮和甲基异丁酮的精制效果明显，其亚磷酸盐含量明显下降，残留溶剂均小于5000mg／kg，丙酮和甲基异丁酮作为双磷酸盐类药物的精制溶剂具有较好的开发和应用价值．

Refining process of bisphosphonates

To avoid the genotoxic risk and solvent compounds of bisphosphonates drug refined by alcohol solvent, non alcohol solvent refining process of bisphosphonates was studied. Iibandronate and pamidronate were refined by non alcohol solvent （acetone and methyl ketone）, the content of Phosphite and residual solvent were detected by titration and gas chromatography. The results show that the refining effect is obvious by acetone and methyl isobutyl ketone with decreasing content of Phosphite and residual solvents is less than 5000 mg/kg. Acetone and methyl isobutyl ketone have good value of development and ~nn[ir~＊; ~：_：__