Identification of the related substances in HZ08 by LC-MS techniques / 中国药学杂志

OBJECTIVE: To identify the related substances in HZ08 by hyphenated techniques. METHODS: A LC-PDA-MS/MS method was developed for the related substances separation and determination. A Sapphire C18(4.6 m×250 mm, 5 μm). column was used with a mixture of methanol and ammonium acetate buffer solution as the mobile phase with gradient elution. HZ08 and the related substances resulted from acid, alkali, and light stress tests were separated under the established HPLC condition and detected with electro-spray positive ionization MS/MS method. The spectra obtained were used for the structures elucidation. RESULTS: Only one related substance was found in HZ08 with the content over 0.1%. Four decomposed substances were found in the acid stress test, one from the alkali and one from the light stress tests. Their structures were elucidated by using the spectra as well as the organic reaction mechanisms. CONCLUSION: The hyphenated LC-MS method is useful for the identification of related substances in pharmaceuticals. The related compounds found in HZ08 are valuable for the manufacturing process optimization and quality control of HZ08. Copyright 2012 by the Chinese Pharmaceutical Association.

Effects of HZ08,a novel P-glycoprotein inhibitor, on the reversal of P-glyco-protein mediated multidrug resistance in nude mice and cytochrome P-450 ac-tivities in rat liver microsomes / 中国药科大学学报

Aim: To evaluate the effects of HZ08, a novel P-glycoprotein inhibitor, on reversing tumor resistance of K562/ADM to adriamycin in nude mice and on the activities of cytochromes P-450 (GYP) isoforms. Methods: Nude mice bearing K562/ADM were injected at different doses of HZ08 with adriamycin for 4 weeks. The tumor weights of HZ08 treatment groups were determined and compared to those of the control and positive groups. In addition, the effects of HZ08 were examined on GYP isoforms-mediated metabolism of specific substrates by GYP isoforms in rat liver microsomes in the presence or absence of HZ08. Results: The tumor weights of HZ08 treatment groups were significantly decreased and HZ08 was a relatively potent inhibitor of CYP3A4, with no significant effects on other isoforms tested. Conclusion: HZ08 has potent effects on reversing P-glycoprotein mediated tumor multidrug resistance in rive with little influence on cytoehrome P-450 activities of rat liver.