中国药理学与毒理学杂志2011，Vol.25Issue(6)：581-585,5.DOI:10.3867/j.issn.1000-3002.2011.06.011
抗辐射药物E0703和代谢物E0703-酮在猕猴体内的药代动力学
Pharmacokinetics of an effective radioprotector E0703 and its metabolite E0703-tone in rhesus monkeys
摘要
Abstract
OBJECTIVE To develop a high performance liquid chromatography-mass spectrometry ( HPLC-MS/MS) method for simultaneous determination of E0703 and its metabolite E0703-tone and investigate pharmacokinetics of E0703 and E0703-tone in rhesus monkeys. METHODS After rhesus monkeys were po given E0703 10 mg·kg-1, blood samples were collected at different time points and pretreated by protein precipitation with acetonitrile. The super-natant diluted with deionized water was separated by HPLC on Capcell Pak C18 MG column. The mass spectrometer was operated in the positive ESI mode and detected by multiple reaction monitoring (MRM), E0703 and it's metabolite E0703-tone were determined by HPLC-MS/MS. Pharmacokinetic parameters of E0703 and E0703-tone were calculated. RESULTS The linear range of E0703 and E0703-tone was both 0.625 -500μg·L-1. The intra- and inter-day precision was <7%. The intra-and inter-day accuracy was both within ±10%. Peak concentration ( cmax) of E0703 and E0703-tone was 14. 7 and 96. 9μg·L-1, respectively. Area under concentrations (AUC) of E0703 and E0703-tone was 173.0 and 1339.7 h·μg22·L-1, and t1/2 was 6. 6 and 11. 8 h, respectively. CONCLUSION A sensitive and precise HPLC-MS/MS method is developed and validated. E0703 is metabolized to ketone metabolites (E0703-tone) in rhesus monkey. The pharmacokinetic behavior of E0703 is similar to that of E0703-tone according to concentration-time profiles. However, cmax and AUC of E0703-tone are much higher than those of E0703.关键词
雌激素衍生物/辐射/药代动力学/液相色谱-质谱法Key words
estrogen derivative/ radiation/pharmacokinetics/ liquid chromatography-mass spectrometry分类
医药卫生引用本文复制引用
贾彦波,王清清,向慎思,杨志晖,杨杰,宋海峰,高月..抗辐射药物E0703和代谢物E0703-酮在猕猴体内的药代动力学[J].中国药理学与毒理学杂志,2011,25(6):581-585,5.基金项目
军队特殊药品专项资助(2008ZXJ001-001) （2008ZXJ001-001）
