百草枯在兔体内的毒物代谢动力学

Toxicokinetics of paraquat in rabbits

目的 建立兔血浆中百草枯的高效液相色谱（HPLC）检测法,研究其在兔体内的毒物代谢动力学.方法 12只雄性H本大耳白兔随机分成2组,单剂量灌胃60 mg/kg或静脉注射6 mg/kg百草枯后不同时间点取血,采用HPLC检测血浆中百草枯的浓度,计算毒物代谢动力学参数及口服生物利用度.结果 HPLC检测血浆中百草枯在0.05～50.00 mg/L的浓度范围内线性关系良好（r=0.9998）,相对回收率为99.41%～102.32%,绝对回收率为83.72%～90.48%,日内、日间精密度的相对标准偏差（RSD）均小于10%.灌胃组百草枯峰浓度为（14.46±2.35）mg/L,达峰时间为（1.63±0.31）h,曲线下面积（0-t）为（177.61±14.62）mg·h/L,曲线下而积（0-∞）为（182.24±14.54）mg·h/L;静脉注射组的峰浓度为（35.13±5.53）mg/L,达峰时间为0.05 h,曲线下面积（0-t）为（121.74±12.30）mg·h/L,曲线下面积（0～∞]为（125.12±12.17）mg·h/L,两组比较,差异有统计学意义（P＜0.05）.口服生物利用度为14.66%±1.55%.灌胃组和静脉注射组的半减期、平均驻留时间比较,差异无统计学意义（P＞0.05）.结论 百草枯口服生物利用度较差,静脉注射与口服给药的半减期无明显差异.建立的HPLC方法简便,准确,灵敏度高,可用于百草枯的检测及毒物代谢动力学研究.

Objective To develop a high performance liquid chromatography method（HPLC） for the determination of paraquat in rabbit plasma and study its toxicokinetics in rabbits. Methods Twelve rabbits were randomly divided into 2 groups with giving oral and intravenous administration of paraquat at a single dose of 60 mg/kg and 6 mg/kg respectively.The plasma paraquat concentrations were determined by HPLC and calculated by DAS pharmacokinetics program. Results The linear range of paraquat in plasma was 0.05 ～50.00 mg/L（r=0.9998 ）. The relative recoveries of the assay were 99.41%～102.32%. The absolute recoveries of the assay were 83.72%～90.48%. Both the intra-day and inter-day validations were less than 10%. For oral administration, the toxicokinetical parameters of paraquat were as follows： Cmax （ 14.46±2.35 ） mg/L, Tmax （ 1.63±0.31 ） h, AUC （0-t）（177.61±14.62） mg·h/L, AUC （0-∞）（182.24±14.54） mg·h/L, While for intravenous administration, the toxicokinetical parameters of paraquat： Cmax（35.13±5.53） mg/L, Tmax 0.05 h, AUC（0-t）（121.74±12.30） mg·h/L, AUC（0-∞） （125.12±12.17）mg·h/L, The difference of these parameters between the two groups had statistical significance （P〈0.05）. The oral bioavailability was （ 14.66± 1.55 ） %. Conclusion The oral bioavailability of paraquat is relatively low. The biological half life of paraquat is relatively long and there is no significant diffrence between oral administration and intravenous on biological half life. This method is simple, sensitive and accurate. It can be used for the investigation of paraquat in rabbits.