β-榄香烯血药浓度测定方法的建立及其药动学研究  

Establishment of Determination Method for Plasma Concentration of β-Elemene and Its Pharmacokinetic Study in Human

作　　者：詹琼[1] 周鑫莉[1] 黄若凡[1] 林浩[1] 葛蒙晰[1] 梁晓华[1] 

机构地区：[1]复旦大学附属华山医院肿瘤科,上海200040

出　　处：《中国药房》2017年第2期173-177,共5页China Pharmacy

基　　金：国家自然科学基金资助项目(No.81302010;81101551);上海市科学技术委员会自然科学基金资助项目(No.13ZR1405000;16ZR1404300)

摘　　要：目的:建立测定人血浆中β-榄香烯浓度的方法,并用于药动学研究。方法:血浆样品经液-液萃取后,以萘为内标,采用气质联用法测定。色谱柱为Rxi-5ms毛细管柱,柱温为150℃,载气为氦气,流速为1.0 m L/min,分流比为0.5∶1,程序升温,进样量为1μL;采用电子轰击离子源,以单离子监测方式进行正离子扫描,选择监测的离子为m/z 93(β-榄香烯)和m/z 128(内标)。选择8例肿瘤患者,单次给予榄香烯注射液10 mg/kg后,采用该法测定给药前后β-榄香烯的血药浓度,采用Win Nonlin 6.0软件计算其药动学参数。结果:β-榄香烯血药浓度在0.163 8~40μg/m L范围内线性关系良好(r=0.999 8,n=5),定量下限为0.163 8μg/m L;日内、日间RSD<10%;平均加样回收率为92.82%~97.75%,平均提取回收率为91.30%~93.31%。8例恶性肿瘤患者单次静脉滴注榄香烯注射液10 mg/kg后,其平均药-时曲线符合权重系数为1/c^2的二室模型,c_(max)为(1.47±0.59)μg/m L,t_(max)为(2.43±0.78)h,AUC0-12 h为(3.52±0.69)μg·h/m L,分布相半衰期为(0.36±0.04)h,消除相半衰期为(1.43±0.80)h,消除速率常数为(0.39±0.06)L^(-1),转运速率常数(k12、k21)分别为(3.21±0.72)和(1.43±0.21)L^(-1)。结论:该方法样品前处理简单,且准确度高、专属性强,适用于β-榄香烯血药浓度的测定及人体药动学的研究。β-榄香烯在人体内吸收快、消除快。OBJECTIVE： To establish a method for the concentration determination of fl-elemene in human plasma, and to study its pharmacokinetics. METHODS： After liquid-liquid extraction, using naphtalin as internal standard, plasma sample was determined by GC-MS. The determination was performed on Rxi-5ms capillary column with column temperature of 150 ℃. The carrier gas was helium at flow rate of 1.0 mL/min with split ratio of 0.5 ： 1 by temperature programming, and sample size was 1 μL. EI and single ion monitoring pattern were used for positive ion scanning with m/z 93（β-elemene） and m/z 128（internal standard）. 8 tumor patients were selected, and were given Elemene injection 10 mg/kg. Plasma concentration of fl-elemene were determined before and after medication. The pharmacokinetic parameters were calculated by WinNonlin 6.3 software. RESULTS： The linear range of β-elemene were 0.163 8-40μg/mL （r=0.999 8, n=5） with quantification limit of 0.163 8 μg/mL; RSDs of intra-day and inter-day were lower than 10 % ; average sample recoveries ranged 92.82 % -97.75 % ; average extraction recoveries ranged 91.30 %-93.31%. After 8 malignant tumor patients were given single intravenous dripping of Elemene injection 10 mg/kg, mean plasma concentration-time curves were in line with two-compartment model with weight coefficient of 1/c2. Pharmacokinetic parameters were as follows： Cmax was（1.47 ± 0.59）μg/mL, tmax was（2.43 ± 0.78）h, AUC0-12 h was（3.52 ± 0.69）μg·h/mL, distribution phase half-life was（0.36 ± 0.04） h, and clearance phase half-life was（1.43 ±0.80）h, elimination rate constant was（0.39 ±0.06）h^-1, and transport rate constant （k12, k21） were （3.21 ± 0.72） and （1.43 ±0.21）h^-1. CONCLUSIONS： The sample preparation method is simple, and the determination method is accurate and specific, and is suitable for plasma concentration and pharmacokinetic study of β-elemene, β-elemene is ab- sorbed and eliminated fast in human.

关 键 词：Β-榄香烯 气质联用法 血药浓度 药动学 

分 类 号：R969.1[医药卫生—药理学]