高效液相色谱法开发、验证及抗肿瘤 HSP90 抑制剂-PU-H71（NSC750424）的杂质特征分析。
HPLC method development, validation and impurity characterization for an antitumor Hsp90 inhibitor-PU-H71 (NSC 750424).
机构信息
SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA.
SRI International, 333 Ravenswood Avenue, Menlo Park, CA 94025, USA.
出版信息
J Pharm Biomed Anal. 2014 Feb;89:34-41. doi: 10.1016/j.jpba.2013.10.021. Epub 2013 Oct 24.
An HPLC method for the assay of the heat shock protein 90 inhibitor, PU-H71 (NSC 750424), has been developed and validated. The stress testing of PU-H71 was carried out in accordance with ICH guidelines Q1A (R2) under aqueous, acidic, alkaline, oxidative, thermolytic and photolytic conditions. The separation of PU-H71 from its impurities and degradation products was achieved within 50min on a Mac-Mod ACE 3 C18 column (150mm×4.6mm i.d., 3μm) with a gradient mobile phase comprising 20-95% acetonitrile in water, with 0.1% trifluroacetic acid in both phases. LC-quadrupole TOF/MS was used to obtain accurate mass data on various components as well as on their fragments for characterization of impurities and degradation products. The proposed HPLC assay method was validated for specificity, linearity (concentration range 0.1-0.3mg/mL, r≥0.9998), accuracy (recovery 99.7-101.1%), precision (intra-lab RSD≤1.39%, inter-lab RSD≤0.91%), sensitivity (LOD 0.08μg/mL), and ruggedness. The developed method was suitable for the assay and stability monitoring of PU-H71 drug substance.
已经开发和验证了一种用于测定热休克蛋白 90 抑制剂 PU-H71（NSC 750424）的 HPLC 方法。根据 ICH 指南 Q1A（R2），在水相、酸性、碱性、氧化、热解和光解条件下对 PU-H71 进行了强制降解试验。在 Mac-Mod ACE 3 C18 柱（150mm×4.6mm id，3μm）上，采用梯度流动相（两相中均含有 0.1%三氟乙酸的 20-95%乙腈），可在 50min 内实现 PU-H71 与其杂质和降解产物的分离。LC-四极杆飞行时间质谱（TOF/MS）用于获得各种成分的准确质量数据以及它们的碎片，以对杂质和降解产物进行表征。所提出的 HPLC 测定方法经过专属性、线性（浓度范围 0.1-0.3mg/mL，r≥0.9998）、准确度（回收率 99.7-101.1%）、精密度（内-实验室 RSD≤1.39%，外-实验室 RSD≤0.91%）、灵敏度（LOD 0.08μg/mL）和耐用性验证。所开发的方法适用于 PU-H71 原料药的测定和稳定性监测。
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