六神丸和雄黄中砷在大鼠体内的药动学研究

Pharmacokinetics of Arsenic of Liushen Pills and Realgar in Rats

分别建立电感耦合等离子体质谱(ICP-MS)和高效液相色谱-电感耦合等离子体质谱联用技术(HPLC-ICP-MS)法测定大鼠全血中总砷含量和不同形态砷的含量。方法学验证结果表明,建立的分析方法线性关系、精密度、重复性和回收率均良好。测定了大鼠灌胃给予等剂量雄黄(125 mg/kg)的六神丸复方和单味雄黄后血中总砷和砷形态的浓度,并采用DAS 2.0软件计算了主要药动学参数,探讨六神丸的配伍对砷毒性影响。结果表明,六神丸组大鼠全血中砷的MRT为12.92 h,较单用雄黄组(MRT=19.54 h)有明显缩短,砷更易被清除,同时血中总砷浓度也更低,砷的主要形态为毒性较低的二甲基砷;而雄黄组中还含有较高浓度毒性较大的亚砷酸盐As(Ⅲ)。提示六神丸中的其他成分可使砷毒性有一定的降低,并促进雄黄中砷由毒性高的形态向毒性低的形态转换。

An inductively coupled plasma mass spectrometry （ICP-MS） method for the determination of total arsenic in blood and an high-performance liquid chromatography （HPLC）-ICP-MS method for the determination of arsenic speciation in blood were established. The results of methodology validation showed that both two determination methods had good linearity, accuracy, reproducibility and recovery. The concentrations of total arsenic and arsenic speciation in blood of rats after ig administration of Liushen pills or realgar at a dose of 125 mg/kg （based on realgar） were determined by ICP-MS and HPLC-ICP-MS. The main pharmacokinetic parameters were calculated by DAS 2.0 software to discuss the effect of compatibility on arsenic toxicity. The results showed that the MRT value of total arsenic in rat blood in Liushen pills group was 12.92 h, which was significantly higher than that ofrealgar group （MRT=19.54 h）. It indicated that arsenic in rat blood of Liushen pills group could be cleared more easily. Moreover, the concentration of total arsenic in Liushen pills group was lower than that in realgar group. The total arsenic was primarily present in the form of dimethyl arsenic acid （DMA） with lower toxicity. While in realgar group, the form of arsenite [As （III）] with high toxicity in blood also had a relative high concentration. It indicated that other components in Liushen pills might decrease the toxicity of arsenic and promote the transition from the high-toxicity form to the low-toxicity form.