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采用液相色谱结合加热电喷雾电离串联质谱法对动物血浆和肝脏中的八种抗凝血灭鼠剂进行多残留分析。

Multi-residue analysis of eight anticoagulant rodenticides in animal plasma and liver using liquid chromatography combined with heated electrospray ionization tandem mass spectrometry.

作者信息

Vandenbroucke Virginie, Desmet Noël, De Backer Patrick, Croubels Siska

机构信息

Ghent University, Faculty of Veterinary Medicine, Department of Pharmacology, Toxicology, Biochemistry and Organ Physiology, Merelbeke, Belgium.

出版信息

J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Jun 15;869(1-2):101-10. doi: 10.1016/j.jchromb.2008.05.011. Epub 2008 May 16.

DOI:10.1016/j.jchromb.2008.05.011
PMID:18502701
Abstract

A sensitive method for the simultaneous quantification of eight anticoagulant rodenticides (brodifacoum, bromadiolone, chlorophacinone, coumatetralyl, difenacoum, difethialone, flocoumafen and warfarin) in animal plasma and liver using liquid chromatography combined with heated electrospray ionization tandem mass spectrometry (LC-HESI-MS/MS) is described. The sample preparation includes a liquid-liquid extraction with acetone. The compound 7-acetoxy-6-(2,3-dibromopropyl)-4,8-dimethylcoumarin is used as an internal standard. Chromatographic separation was achieved using a Nucleodur C18 gravity column. Good linearity was observed up to 750 ng mL(-1) for chlorophacinone and up to 500 ng mL(-1) for the other compounds in plasma. In liver, good linearity was seen up to 500 ng g(-1) for brodifacoum, chlorophacinone, difenacoum and difethialone and up to 750 ng g(-1) for the other compounds. Depending on the compound, a level of 1 or 5 ng mL(-1) could be quantified fulfilling the criteria for accuracy and precision and was therefore set as limit of quantification of the method in plasma. In liver, the limit of quantification was set at 250 ng g(-1) for coumatetralyl and warfarin and at 100 ng g(-1) for the other compounds. In plasma, the limit of detection varied from 0.07 ng mL(-1) for flocoumafen to 3.21 ng mL(-1) for brodifacoum. In liver, the limit of detection varied from 0.37 ng g(-1) for warfarin to 4.64 ng g(-1) for chlorophacinone. The method was shown to be of use in a pharmacokinetic study after single oral administration to mice and in the confirmation of suspected poisoning cases in domestic animals.

摘要

描述了一种使用液相色谱结合加热电喷雾电离串联质谱法(LC-HESI-MS/MS)同时定量动物血浆和肝脏中八种抗凝血灭鼠剂(溴敌隆、溴鼠灵、氯鼠酮、杀鼠迷、敌鼠、氟鼠酮、氟虫腈和华法林)的灵敏方法。样品制备包括用丙酮进行液-液萃取。化合物7-乙酰氧基-6-(2,3-二溴丙基)-4,8-二甲基香豆素用作内标。使用Nucleodur C18重力柱实现色谱分离。在血浆中,氯鼠酮的线性范围高达750 ng mL(-1),其他化合物的线性范围高达500 ng mL(-1)。在肝脏中,溴敌隆、氯鼠酮、敌鼠和氟鼠酮的线性范围高达500 ng g(-1),其他化合物的线性范围高达750 ng g(-1)。根据化合物的不同,能够定量达到1或5 ng mL(-1)的水平,满足准确度和精密度标准,因此将其设定为该方法在血浆中的定量限。在肝脏中,杀鼠迷和华法林的定量限设定为250 ng g(-1),其他化合物的定量限设定为100 ng g(-1)。在血浆中,检测限从氟虫腈的0.07 ng mL(-1)到溴敌隆的3.21 ng mL(-1)不等。在肝脏中,检测限从华法林的0.37 ng g(-1)到氯鼠酮的4.64 ng g(-1)不等。该方法在小鼠单次口服给药后的药代动力学研究以及家畜疑似中毒病例的确认中显示出实用性。

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