摘要
目的建立测定盐酸洛拉曲克血浆药物浓度的高效液相色谱-质谱联用分析方法,研究盐酸洛拉曲克在小鼠体内的药代动力学和绝对生物利用度。方法C57小鼠静脉(50mg/kg)或口服(200mg/kg)给予盐酸洛拉曲克,在给药后不同时间取血,分离血浆,用高效液相色谱-质谱联用法测定血浆中盐酸洛拉曲克浓度。用DAS软件计算盐酸洛拉曲克的药代动力学参数,根据口服和静注的药时曲线下面积之比来计算绝对生物利用度。结果盐酸洛拉曲克在0.01～40mg/L浓度范围内线性关系良好(r=0.9995,P<0.001),样品在血浆中的回收率大于85%,日内和日间RSD小于15%。小鼠静注50mg/kg盐酸洛拉曲克后药代动力学参数半衰期、药-时曲线下面积、分布系数、清除率分别为(3.020±0.017)h、(89.972±0.425)mg·L-1·h-1、(0.831±0.106)L/kg、(0.556±0.093)L·h-1·kg-1;小鼠口服200mg/kg盐酸洛拉曲克后药代动力学参数半衰期、药-时曲线下面积、达峰时间、峰浓度分别为(5.046±0.191)h、(84.893±9.923)mg·L-1·h-1、(1.000±0.012)h、(18.000±0.014)mg/L。经计算盐酸洛拉曲克在小鼠体内的绝对生物利用度为23.58%。结论用高效液相色谱-质谱联用方法测定的盐酸洛拉曲克在小鼠体内的绝对生物利用度为该药的口服制剂的研发提供了实验依据。
Objective To establish a methods based on high-performance liquid chromatogram-mass spectrum for measuring the plasma concentration ofnolatrexed dihydrochloride and investigate the pharmacokinetic profile and absolute bioavailability of the drug in mice. Methods Nolatrexed dihydrochloride were injected intravenously at 50 mg/kg or administered orally at 200 mg/kg in mice, and blood samples were collected at various time points following drug administration. The plasma concentration of nolatrexed dihydrochloride in mice was determined using high-performance liquid chromatogram-mass spectrum. The pharmacokinetic parameters were calculated using DAS sol, rare, and the absolute bioavailability of orally and intravenously administered was assessed according to the ratio of their area under the curve （AUC）. Results The method showed good linear relationship within the drug concentration range of 0.01-40 mg/L （r=0.9995, P〈0.001）. The recovery ofnolatrexed dihydrochloride from the mouse plasma was more than 85%, and the intra- and inter-day precision expressed as the relative standard deviation was less than 15%. The half-life （T1/2）, AUC, distribution factor and plasma clearance （CL） for intravenously administered nolatrexed dihydrochloride （50 mg/kg） were 3.020±0.017 h, 89.972±0.425 mg· L^-1· h^-1, 0.831±0.106 L/kg, and 0.556±0.093 L· h^-1 ·kg^-1, respectively. The T1/2, AUC, peak time （Tmax and peak concentration （Cmax） for orally administered drug were 5.046± 0.191 h, 84.893±9.923 mg·L^-1·h^-1, 1.000±0.012 h, and 18.000±0.0140 mg/L, respectively. The absolute bioavailability of nolatrexed dihydrochloride in mice was 23.58%. Conclusion The absolute bioavailability of nolatrexed dihydrochloride in mice determined in this study provides an experimental basis for development of the oral preparation of the drug.
出处
《南方医科大学学报》
CAS
CSCD
北大核心
2008年第11期1993-1995,共3页
Journal of Southern Medical University
基金
广州市粤港合作重点课题(GK0601005)
关键词
盐酸洛拉曲克
高效液相色谱-质谱联用
药代动力学
生物利用度
nolatrexed dihydrochloride
high performance liquid chromatogram-mass spectrum
pharmacokinetics
absolute bioavailability
