半合成紫杉醇工艺杂质研究

Study on the Process-related Impurities of Semi-synthetic Paclitaxel

摘要: 目的研究半合成紫杉醇工艺杂质，结合合成路线推测工艺杂质的来源。方法利用硅胶柱色谱制备分离了kingston半合成路线中的4个工艺杂质，通过质谱及核磁共振波谱鉴定化学结构。结果 4个工艺杂质分别是5β,20-环氧-1,7β-二羟基-9-羰基紫杉-11-烯-2α,4,10β,13α-四取代基4,10-二乙酰氧基2-苯甲酰氧基13-(2R,3S)-3-氨基-2-苯甲酰氧基-3-苯基丙酸酯(1)、7-乙酰基紫杉醇(2)、13-Tes-巴卡亭Ⅲ(3)、7-表紫杉醇(4)。结论杂质(1)尚未被美国药典和欧洲药典收载，研究结果为半合成紫杉醇的质量控制提供了依据。

Abstract: OBJECTIVE To study the process-related impurities of semi-synthetic paclitaxel and discuss the formation mechanism according to the synthetic route. METHODS The process-related impurities of semi-synthetic paclitaxel in kingston route were isolated by silica gel column chromatography and identified by mass spectrometry and nuclear magnetic resonance analysis. RESULTS Their structures were 5β,20-epoxy-1,7β-dihydroxy-9-oxotax-11-ene-2α,4,10β, 13α-tetrayl 4, 10-diacetate 2-benzoate 13-(2R,3S)-3-amino-2-benzoate-3-phenylpropanaoate(1), 7-acetylpaclitaxel(2), 13-Tes-baccatin Ⅲ(3), 7-epipaclitaxel(4), respectively. CONCLUSION Impurity(1) has not been recorded by United States Pharmacopoeia and European Pharmacopoeia. The result could provide a basis for quality control of semi-synthetic paclitaxel.