An UPLC-MS/MS method to monitor Estriol injection and comparison of pharmacokinetic characteristics after irradiation

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。