GC-MS测定大鼠血浆中反式氧化樟脑含量及其体内药动学研究

Determination of trans-π-oxocamphor Concentration in Rat Plasma by GC-MS and the in vivo Pharmacokinetics Study

目的测定大鼠血浆中反式氧化樟脑的含量并研究其在大鼠体内药动学。方法采用液液萃取法处理血浆样品,以甲苯为内标,采用气质联用法测定。色谱柱为HP-5MS毛细管柱,载气为氦气,流速为1.11 mL·min^-1;进样量1μL,分流进样,程序升温;采用电子轰击离子源,以单离子监测方式进行正离子扫描。6只大鼠静脉给予氧化樟脑注射液后采血,测定血药浓度,采用DAS 2.1.1拟合房室模型并计算药动学参数。结果血浆反式氧化樟脑浓度在0.1~10.0μg·mL^-1范围内线性关系良好;定量下限为0.1μg·mL^-1;绝对回收率平均在76.94%~85.31%,基质效应平均值在94.42%~98.50%,批内、批间精密度RSD1.45%~10.36%。大鼠的药时曲线符合二房室模型,反式氧化樟脑在大鼠体内消除迅速,主要药动学参数为AUC(0-t)为(20.459±2.034)mg·L^-1·min,t1/2z为(6.938±3.093)min,CLz为(0.175±0.017)L·min^-1·kg^-1,Cmax为(5.604±0.641)mg·L^-1。结论该方法样品前处理简单,且准确度高、专属性强,适用于反式氧化樟脑的血药浓度测定,可为其人体内药动学研究提供参考。

Objective To establish a method for the determination of trans-π-oxocamphor concentration in rat plasma and investigate its pharmacokinetic profile in rat.Methods The plasma samples were processed by a liquid-liquid extraction,and the samples were analyzed by GC-MS using toluene as an internal standard.The determination was performed on a HP-5MS capillary column using helium as the carrier gas at a flow rate of 1.11 mL·min^-1.The sample size was 1μL under the programmed temperature control.Electron bombardment ion source was used for positive ion scanning in a single ion monitoring pattern.Plasma of six rats was sampled and tested after intravenous administration of trans-π-oxocamphor,and DAS 2.1.1 was used to evaluate the pharmacokinetic parameters.Results The linear range of trans-π-oxocamphor concentration was in 0.1~10.0μg·mL^-1 with LLOQ of 0.1μg·mL^-1.The average absolute recovery rate was 76.94%~85.31%with matrix effects of 94.42%~98.50%.The RSDs of intra-day and inter-day ranged from 1.45%to 10.36%.The pharmacokinetics study showed the two-compartment model was suitable for profiling the concentration-time curve of trans-π-oxocamphor,which demonstrated its quick elimination profile.The main pharmacokinetic parameters were obtained,including AUC(0-t)=20.459±2.034 mg·L^-1·min,t1/2z=6.938±3.093 min,CLz=0.175±0.017 L·min^-1·kg^-1,and Cmax=5.604±0.641 mg·L^-1.Conclusion The established method was proved to be simple,sensitive and accurate,which could be used to determine the plasma concentration of trans-π-oxocamphor in rat.And it can provide a reference for the study of pharmacokinetics in human.