超高效液相色谱-质谱法比较黑顺片单煎液及其复方煎煮液中次乌头碱在大鼠体内的吸收

摘要

An ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF MS) method was developed for the determination of hypaconitine in the plasma of the rats administered with Heishunpian (HSP) decoction, Zhufu (ZF) decoction and Gancaofuzi (GF) decoction, separately.Hypaconitine and the internal standard were separated on a ZORBAX Extend-C18 column.The concentration-time curve of hypaconitine in the plasma was protracted, and pharmacokinetic parameters were calculated, then the pharmacokinetic comparison of hypaconitine between HSP, ZF and GF was carried out for the first time.The results of the methodological test showed that the plasma concentration of hypaconitine presented good linear relationship in the range of 0.02 - 10 ng/mL.The results of the sample determination showed that the absorptive degree of hypaconitine from ZF decoction in the plasma was lower than that from HSP decoction, while the absorptive degree of hypaconitine from GF decoction in plasma was higher than that from HSP decoction.It was deduced that some components in ZF decoction can restrain the absorption of hypaconitine in plasma, and some components in GF decoction may promote the absorption of hypaconitine in plasma, and the difference in drug effects between ZF decoction and GF decoction may derive from the different absorptive degrees of hypaconitine in plasma.The pharmacokinetic property of hypaconitine was proposed to be non-linear dynamics on the basis of the drug elimination half life ( T1/2 ) and the area under the plasma concentration-time curve (AUC).%为了研究有毒中药中主要成分的体内吸收,以黑顺片单煎液及其复方煎煮液"术附汤"和"甘草附子汤"灌胃大鼠血浆中的次乌头碱为检测指标,建立了血浆中次乌头碱的超高效液相色谱-四极杆飞行时间质谱(UPLC/Q-TOF MS)检测方法,并采用内标法对其进行了含量测定,绘制了血药浓度-时间曲线,计算了药动学参数.方法学考察结果表明血中次乌头碱在0.02～10 ng/mL范围内呈现良好的线性关系;样品测定结果表明,"术附汤"中的某种或某些成分抑制了次乌头碱的体内吸收,而"甘草附子汤"中的某种或某些成分促进了次乌头碱的体内吸收,两复方功效差异可能来源于次乌头碱在体内吸收程度的不同.由3种煎煮液中次乌头碱的消除半衰期(T<,1/2>)及血药浓度-时间曲线下面积(AUC)值推测次乌头碱在大鼠体内的转运过程为非线性动力学过程.