摘要
目的:建立人血浆中倍他米松17-丙酸酯(B17P)的LC-MS/MS测定方法,并研究其在健康人体内的药动学特征。方法:采用Agilent Zorbax C18(2.1 mm×100 mm,3.5μm)色谱柱,以甲醇-水(88:12)为流动相,流速0.15 ml·min^(-1);电喷雾(ESI)离子源,正离子电离模式,多反应离子监测(MRM)的扫描方式,B17P和二丙酸倍氯米松(内标,IS)的检测离子对分别选择为m/z 471.1→397.1和543.2→433.1。结果:B17P的线性范围为0.02～2.0 ng·ml^(-1)(r=0.999 3,n=5),定量下限为0.02 ng·ml^(-1),日内和日间精密度(RSD)均小于10.9%,提取回收率在70%左右,方法回收率均在94.5～106.6%范围内。B17P的t_(1/2)为(82.5±17.3)h,C_(max)为(0.73±0.18)h,AUC_(0～1)为(63.9±13.6)ng·h·ml^(-1)。结论:该法简便、快速、灵敏、准确,适用于B17P血药浓度测定及其人体药动学研究。
Objective： To establish an LC-MS/MS method for the determination of betamethasone-17-monopropionate （B17P） in human plasma and study its pharmacokinetics in human volunteers. Method： Agilent Zorbax C18 （2. 1 mm × 100 mm,3.5 μm） chromatographic column was used, the mobile phase consisted of methanol/water （88： 12） and the flow rate was 0. 15 ml· min^-1. ESI and MRM with positive ionization model were applied. The mass transition pairs of m/z 471.1→397. 1 and m/z 543.2→433.1 were used to detect B17P and beclomethasone dipropionate （the internal standard, IS）, respectively. Result： The standard curve of B17P was linear over the concentration range of 0. 02-2.0 ng·ml^ - 1 （ r = 0. 999 3, n = 5 ）. The quantitative lower limit of B 17 P was 0. 02 ng·ml ^- 1. Intraday and inter-day RSDs of B17P were both less than 10. 9%, the extraction recovery was about 70% and the relative recoveries were within 94. 5-106. 6%. The major pharmacokinetic parameters of B17P were as the follows：t1/2 of （82. 5 ± 17. 3） h,Cmax of （0. 73 ± 0. 18） h and AUC（0-4） of （63.9 ± 13.6） ng·h·ml^-1. Conclusion： This method is simple,fast,sensitive and accurate. It can be used in the determination of B17P in human plasma and clinical pharmacokinetics studies.
出处
《中国药师》
CAS
2011年第10期1423-1426,共4页
China Pharmacist
