溴苯腈在兔的血药浓度GC-MS法测定及其药动学研究

Study of toxicokinetics of bromoxynil in rabbits

目的:建立兔血浆溴苯腈检测的气相色谱-质谱分析的方法,研究溴苯腈在兔体内的毒代动力学。方法:雄性日本大耳白7只,予30 mg.kg-1溴苯腈原药灌胃,分别于灌胃前及给药后72 h内多点抽取静脉血。用气相色谱-质谱联用法(GC-MS)测定血浆中溴苯腈浓度。结果用DAS软件进行分析,计算毒代动力学参数。结果:兔30 mg.kg-1溴苯腈ig后t1/2ke为11.327±3.043 h,Tmax为5.571±1.134 h,Cmax为109.943±43.486 mg.L-1,AUC0-tn为2275±959 mg.L.h-1,AUC0-∞为2315±980 mg.L.h-1,MRT0-tn为16.9±2.5 h,MRT0-∞为18.1±2.9 h。结论:溴苯腈经口吸收后的毒代过程符合一级吸收一室开放模型,吸收及消除均较慢。本研究采用的气相色谱-质谱联用法检测血浆溴苯腈浓度准确、快速、简便。

AIM： To develop a gas chromatographymass spectrography method for the determination of Bromoxynil in rabbit plasma, and to study the toxicokinetics of Bromoxynil in rabbits. METHODS： Seven male rabbits were involved in the study. Each subject received a single dose of 30 mg·kg^-1 Bromoxynil tested formulation. Blood samples were conducted consequently within 72 hours. The plasma Bromoxynil concentrations were determined by GC-MS. The plasma Bromoxynil concentration were calculated by ADS and calculated the toxicokinetics parameters. RESULTS： After a single dose of 30 mg·kg^-1 tested formulation, the oxicokinetics parameters of Bromoxynil were as following： t1/2ke was 11 ± 3 hours,Tmax5.6 ± 1.2 hours, Cmax, 110 ± 43 mg·L^-1 , AUC0-tn 2275 ± 959 mg·L^-1·h^-1 and AUC0-∞ 2315 ± 980 mg·L^-1·h^-1, MRT0-tn 16.9 ± 2.5 hours, and MRT0-∞ 18.1 ± 2.9 hours. CONCLUSION： After 30 mg· kg^-1 ig administration demonstrates that plasma Bmmoxynil concentration against time profile is fitted well to the one- compartment open model with 1st order absorption. Absorption and elimination of Bromoxynil in rabbits were all slow. The method for determination of Bromoxynil concentration in plasma by GC-MS is simple, sensitive, and accurate.