溴苯腈在兔的血药浓度 GC-MS 法测定及其药动学研究

中国临床药理学与治疗学 ›› 2006, Vol. 11 ›› Issue (1): 99-103.

溴苯腈在兔的血药浓度 GC-MS 法测定及其药动学研究

刘晓, 卢中秋¹, 胡国新², 徐雪松³ , 林宏亮³

温州医学院附属第一院八院区急诊科, ¹附属第一医院急诊科, ²药学院, 温州 325000, 浙江 ; ³温州市公安局刑侦支队, 温州 325000, 浙江

收稿日期:2005-09-17 修回日期:2005-11-17 出版日期:2006-01-06 发布日期:2020-10-23
通讯作者: 卢中秋, 通讯作者, 男, 主任医师, 硕士生导师, 研究方向:危重病急救医学, 急性中毒毒理与解毒研究。
作者简介:刘晓, 女, 主治医师, 硕士, 研究方向:危重病急救医学, 急性中毒毒理与解毒研究。 Tel:( 0) 13634244407 E-mail:alishaliu@sina .com 卢中秋, 通讯作者, 男, 主任医师, 硕士生导师, 研究方向:危重病急救医学, 急性中毒毒理与解毒研究。
基金资助:
温州市科技局计划项目资助( №Y2004A134)

Study of toxicokinetics of bromoxynil in rabbits

LIU Xiao, LU Zhong-qiu¹ , HU Guo-xin², XU Xue-song³ , LIN Hong-liang³

Eighth Branch of the First Affiliated Hospital of Wenzhou Medical College, Wenzhou 325027, Zhejiang, China ;¹The First Affiliated Hospital of Wenzhou Medical College,²Department of Pharmacology , Wenzhou Medical College, Wenzhou 325027 , Zhejiang, China ;³Wenzhou Public Security Burea, Wenzhou 325027 , Zhejiang, China

Received:2005-09-17 Revised:2005-11-17 Online:2006-01-06 Published:2020-10-23

摘要/Abstract

摘要： 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 t_{1 /2ke} 为 11 .327 ±3 .043 h, T_max 为 5 .571 ±1 .134 h, C_max为 109 .943 ±43 .486 mg·L^-1 , AUC_{0 -tn} 为 2275 ± 959 mg·L·h ^-1 , AUC_0-∞ 为 2315 ±980 mg·L·h^-1, MRT_{0 -tn}为 16 .9 ±2 .5 h,MRT_{0 -∞} 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。

关键词: 溴苯腈 , 毒动学 , 气相色谱-质谱联用, 中毒

Abstract: AIM:To develop a gas chromatography- mass spectrography method for the determination of Bro- moxynil in rabbit plasma, and to study the toxicokinetics of Bromoxynil in rabbits .METHODS:Seven male rab- bits 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 deter- mined 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 :t_{1 /2ke} was 11 ±3 hours, · 102 · Chin J Clin Pharmacol Ther 2006 Jan;11( 1) T_max 5 .6 ±1 .2 hours, C_max 110 ±43 mg·L^-1 , AUC_{0 -tn} 2275 ±959 mg·L^-1·h^-1 and AUC_{0 -∞} 2315 ±980 mg·L ^-1·h^-1 , MRT_0-tn 16 .9 ±2 .5 hours, and MRT_{0 -∞} 18 .1 ±2 .9 hours .CONCLUSION:After 30 mg·kg^-1 ig administration demonstrates that plasma Bromoxynil concentration against time profile is fitted well to the one- compartment open model with 1st order absorption .Ab- sorption and elimination of Bromoxynil in rabbits were all slow.The method for determination of Bromoxynil con- centration in plasma by GC-MS is simple, sensitive, and accurate .

Key words: Bromoxynil , toxicokinetics , gas chrom- atography-mass spectrum ( GC-MS) , intoxication

中图分类号:

R965

刘晓, 卢中秋, 胡国新, 徐雪松, 林宏亮. 溴苯腈在兔的血药浓度 GC-MS 法测定及其药动学研究[J]. 中国临床药理学与治疗学, 2006, 11(1): 99-103.

LIU Xiao, LU Zhong-qiu , HU Guo-xin, XU Xue-song , LIN Hong-liang. Study of toxicokinetics of bromoxynil in rabbits[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2006, 11(1): 99-103.

参考文献

1 Topp E, Xun LY, Orser CS .Biodegradation of the herbicide bro- moxynil ( 3, 5-dibromo-4-hydroxybenzonitrile) by purified penta- chlorophenol hydroxylase and whole cells of Flavobacterium sp. strain ATCC 39723 is accompanied by cyanogenesis[ J] .Appl Environ Microbiol, 1992;58 :502-6
2 McBride KE, Kenny JW, Stalker DM.Metabolism of the herbi- cide bromoxynil by Klebsiella pneumoniae subsp ozaenae[ J] . Appl Environ Microbiol, 1986;52 :325-30 3 王维信, 王敖格, 王健春.临床药物代谢动力学的基本理论[ A] .见:王维信, 王敖格, 王健春主编.临床药物代谢动力学[ M] .第一版 .北京:学苑出版社, 1998:24
4 Semchuk K, McDuffie H, Senthilselvan A, Cessna A, Irvine D.Body mass index and bromoxynil exposure in a sample of ru- ral residents during spring herbicide application[ J] .J Toxicol Environ Health A, 2004 ;67:1321-52
5 Dijkman E, Mooibroek D, Hoogerbrugge R, Hogendoorn E, Sancho JV, Pozo O, et al .Study of matix effect on the direct trace analysis of acidic pesticide in water using various liquid chromatographic modes coupled to tandem mass spectrometic de- tection[ J] .J Chromatogr A, 2001;926 :113-25
6 余永红, 李文明, 孙淑君, 陈志申.溴苯腈辛酸酯原药的气相色谱分析[ J] .河南化工, 1997;7 :21-2
7 Henriksen T, Svensmark B, Lindhardt B, Juhler RK.Analysis of acidic pesticides using situ derivatization with alklchloroformate and solid-phase microextraction ( SPME) for GC-MS[ J] .Chem- osphere, 2001;44 :1531-9
8 张永忠, 李有, 母灿先.溴苯腈样品中杂质的定性、定量研究[ J] .农药, 2001;40 :20-1
9 Semchuk KM, McDuffie HH, Senthilselvan A, Dosman JA, Cessna AJ, Irvine DG .Factors associated with detection of bro- moxynil in a sample of rural residents[ J] .J Toxicol Environ Health A, 2003 ;66:103-13

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