| 1 | Evaluation of the metabolism of PEP06,an endostatin-RGDRGD 30-amino-acid polypeptide and a promising novel drug for targeting tumor cells显示文摘PEP06 is a novel endostatin-Arg-Gly-Asp-Arg-Gly-Asp(RGDRGD)30-amino-acid polypeptide featuring a terminally fused RGDRGD hexapeptide at the N terminus.The active endostatin fragment of PEP06 directly targets tumor cells and exerts an antitumoral effect.However,little is known about the kinetics and degradation products of PEP06 in vitro or in vivo.In this study,we investigated the in vitro metabolic stability of PEP06 after it was incubated with living cells obtained from animals of different species;we further identified the degradation characteristics of its cleavage products.PEP06 underwent rapid enzymatic degradation in multiple types of living cells,and the liver,kidney,and blood play important roles in the metabolism and clearance of the peptides resulting from the molecular degradation of PEP06.We identified metabolites of PEP06 using full-scan mass spectrometry(MS)and tandem MS(MS2),wherein 43 metabolites were characterized and identified as the degradation metabolites from the parent peptide,formed by successive losses of amino acids.The metabolites were C and N terminal truncated products of PEP06.The structures of 11 metabolites(M6,M7,M16,M17,M21,M25,M33,M34,M39,M40,and M42)were further confirmed by comparing the retention times of similar full MS spectrum and MS2 spectrum information with reference standards for the synthesized metabolites.We have demonstrated the metabolic stability of PEP06 in vitro and identified a series of potentially bioactive downstream metabolites of PEP06,which can support further drug research. | Liyun Niu Huiyu Zhou Yueru Lian Ya Gao Yulu Liu Ruolan Gu Zhuona Wu Xiaoxia Zhu Hui Gan Zhiyun Meng Guifang Dou | 2022 | Journal of Pharmaceutical Analysis2022，12，5： | 0 |
| 2 | An UPLC-MS/MS method to monitor Estriol injection and comparison of pharmacokinetic characteristics after irradiation显示文摘Objective:To develop an UPLC-MS/MS method for the accurate quantification of Estriol(E3),a new radioprotective agent,and observe the variation in pharmacokinetic characteristics of E3 after irradiation.As a hormone drug,the gender differences of E3 metabolism were also concerned here.Methods:Various chromatographic and mass spectrometric conditions of E3 were optimized.The specificity,linearity,precision and accuracy of UPLC-MS/MS method were validated.Twenty SD rats,half male and half female,were administered with intramuscular(im)injection of 2.7 mg/kg E3,and then divided randomly into two groups,sham-irradiated group(Con)and irradiated group(IR).IR group was irradiated to 7 Gy ofγ-rays.Blood samples were collected at different times post-irradiation and E3 concentrations were detected.The changes of concentration-time variation and pharmacokinetic parameters for E3 after irradiation were investigated,together with metabolic differences between male and female rats.Results:The range of the calibration curve of UPLC-MS/MS for E3 was 1.00–200.0 ng/mL.Con group reached maximum concentration(Cmax)(77.57±18.71)ng/mL at(0.68±0.29)h(Tmax)after im injection.The drug concentration-time profiles and pharmacokinetic parameters of E3 were consistent before and after irradiation.The areas under time curve(AUC0-t)of E3 were(353±74)h⋅ng/mL for Con group,and(299±74)h⋅ng/mL for IR group(P>0.05).There were also no statistical differences in pharmacokinetic parameters between female and male rats.The elimination half-lifes(T1/2)of males and females were(3.02±0.68)h and(3.01±0.42)h in Con group,and(3.64±0.51)h and(3.38±0.60)h in IR group,respectively(P>0.05).Conclusion:A rapid and sensitive UPLC-MS/MS method for determination of E3 was established.The pharmacokinetic characteristics of E3 in rat were not affected by 7 Gy irradiation and gender differences.This study provided a theoretical basis for the development and application of new radiation injury treatment drug。 | Hanming Zhang Zhiyun Meng Tong Ye Taoyun Liu Jian Li Fei Ma Ruolan Gu Xiaoxia Zhu Zhuona Wu Guifang Dou Hui Gan | 2021 | Radiation Medicine and Protection2021，2，2： | 0 |
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