| Autor: |
Hanming Zhang, Zhiyun Meng, Tong Ye, Taoyun Liu, Jian Li, Fei Ma, Ruolan Gu, Xiaoxia Zhu, Zhuona Wu, Guifang Dou, Hui Gan |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
Radiation Medicine and Protection, Vol 2, Iss 2, Pp 72-78 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2666-5557 |
| DOI: |
10.1016/j.radmp.2021.05.001 |
| Popis: |
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 of γ-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. |
| Databáze: |
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| Externí odkaz: |
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