呋喃丹及其代谢产物呋喃酚在大鼠体内的死后分布研究

Postmortem distribution of carbofuran and its main metabolite benzofuranol in rats

建立生物样品中呋喃丹及其代谢物呋喃酚的高效液相色谱-质谱联用内标分析法,研究两者大鼠体内的死后分布规律。灌胃给予大鼠4倍LD_(50)(44 mg/kg)浓度为1. 8 mg/m L自制呋喃丹混悬液,死亡后分别于0,12,24,48,72和96 h取材,HPLC-MS/MS法测定心血、心、肝、脾、肺、肾、脑、左下肢肌、胃壁等检材中呋喃丹及呋喃酚含量。结果显示,死后0 h呋喃丹在大鼠体内分布如下:胃壁>肺、肝>肾、脾>心脏、心血、脑,并逐渐从胃壁、肺及心血向肝、肾、心及骨骼肌中转移。而呋喃酚在大鼠体内分布如下:胃壁>心血>肝、肾>脾、肌肉、肺、脑>心,心血、心、肝、脾、肾中的呋喃酚浓度死后显著上升(P <0. 05)。呋喃丹的降解及呋喃丹在不同组织间的扩散迁移共同导致了呋喃丹及其代谢产物呋喃酚组织浓度的死后变化。本研究建立的呋喃丹及呋喃酚组织含量HPLC-MS/MS检测方法及获得的死后分布规律可作为呋喃丹中毒死亡案件的法医学鉴定提供参考,并且为全面正确采取检材进行毒物分析提供方向。

An HPLC-MS/MS method using carbaryl as the internal standard substance was established for qualitative detection and quantitative determination of carbofuran and its main metabolite benzofuranol in bio-samples to study their postmortem distribution in rats.The rats were poisoned dead by intragastric administration of carbofuran suspension at the concentration of1.8mg/mL,which was4times of the LD50(44mg/kg).Then the rats were dissected at0,12,24,48,72and96hours after death to collect the their specimen(heart,liver,spleen,lung,kidney,brain,muscle,stomach,blood)and the carbofuran concentration were determined using HPLC-MS/MS method.The results showed that at0h after death,the carbofuran was distributed in rats was as follows:stomach>lung or liver>kidney or spleen>muscle>heart or heart blood or brain and transferred from stomach,lung and heart blood to liver,kidney and muscle over time,while the benzofuranol was distributed as follows:stomach>heart blood>liver or kidney>spleen or muscle or lung or brain>heart,and the concentration of benzofuranol in heart blood,heart,liver,spleen,and kidney had significant increase(P<0.05)over time.The postmortem concentration change of carbofuran and benzofuranol could be attributed to the degradation of carbofuran and the trans-tissues diffusion of carbofuran and benzofuranol.The postmortem distribution manner of carbofuran and benzofuranol and their HPLC-MS/MS analysis method could be applied to the forensic identification and help taking samples for toxicology analysis.