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HPLC method development, validation and impurity characterization for an antitumor Hsp90 inhibitor-PU-H71 (NSC 750424).

ABSTRACT: 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., 3?m) 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 0.08?g/mL), and ruggedness. The developed method was suitable for the assay and stability monitoring of PU-H71 drug substance.

SUBMITTER: Liu M

PROVIDER: S-EPMC3954645 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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HPLC method development, validation, and impurity characterization of a potent antitumor indenoisoquinoline, LMP776 (NSC 725776).

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The purine scaffold HSP90 inhibitor PU-H71 induces specific changes in gene expression in DLBCL xenografts.

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2009-11-15 | GSE13401 | GEO

First-in-human study of the epichaperome inhibitor PU-H71: clinical results and metabolic profile.

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The purine scaffold Hsp90 inhibitor PU-H71 sensitizes cancer cells to heavy ion radiation by inhibiting DNA repair by homologous recombination and non-homologous end joining.

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Isolation and Characterization of an Unknown Process-Related Impurity in Furosemide and Validation of a New HPLC Method.

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| S-EPMC10005432 | biostudies-literature

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