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Simple validated method of LC-MS/MS determination of BZ agent in rat plasma samples.
Drug Testing and Analysis ( IF 2.9 ) Pub Date : 2020-01-10 , DOI: 10.1002/dta.2742
David Herman 1 , Alzbeta Dlabkova 1 , Lenka Cechova 1 , Nela Vanova 2 , Jan Misik 1 , Daniel Jun 1 , Jana Zdarova Karasova 1
Affiliation  

Agent BZ (3‐quinuclidinyl benzilate) is a centrally acting synthetic anticholinergic agent, considered as a potential military incapacitating chemical warfare agent. Despite its significance as a model compound in pharmacological research and its potential misuse in chemical attacks, few modern analytical methods for BZ determination in biological samples have been published. The goal of the present work is to develop and validate a sensitive and rapid LC–MS/MS method for the determination of agent BZ in rat plasma. The sample preparation was based on solid‐phase extraction on C‐18 cartridges. The reversed‐phase HPLC coupled with the mass spectrometer with electrospray ionization in the positive ion‐selective reaction monitoring mode was employed in the BZ analysis. Atropine was used as an internal standard. The presented method is selective, accurate, precise, and linear (r2 = 0.9947) in a concentration range from 0.5 ng/mL to 1 000 ng/mL and sensitive enough (limit of detection 0.2 ng/mL; limit of quantification 0.5 ng/mL) to determine the BZ plasma levels in rats exposed to 2 mg/kg and 10 mg/kg of BZ. The highest level of BZ in plasma was observed 5 minutes after intramuscular administration (154.6 ± 22.3 ng/mL in rats exposed to 2 mg/kg of BZ and 1024 ± 269 ng/mL in rats exposed to 10 mg/kg). After 48 h, no BZ was observed at detectable levels. This new method allows the detection and quantification of BZ in biological samples after exposure of an observed organism and it will be further optimized for other tissues to observe the distribution of BZ in organs.

中文翻译:

LC-MS / MS测定大鼠血浆样品中BZ剂的简单有效方法

药剂BZ(3-奎宁环戊基苯甲酸酯)是一种中枢作用的合成抗胆碱能药,被认为是潜在的军用无能化学战剂。尽管它在药理研究中作为模型化合物具有重要意义,并且在化学攻击中可能被滥用,但很少有用于测定生物样品中BZ的现代分析方法。本工作的目的是开发和验证一种灵敏,快速的LC-MS / MS方法,用于测定大鼠血浆中的BZ药剂。样品制备基于在C-18小柱上的固相萃取。在BZ分析中采用了反相HPLC结合质谱仪并在正离子选择性反应监测模式下进行电喷雾电离。阿托品被用作内标。提出的方法是选择性的,2 = 0.9947)的浓度范围为0.5 ng / mL至1000 ng / mL,并且足够灵敏(检测极限0.2 ng / mL;定量极限0.5 ng / mL)以确定暴露于2的大鼠的BZ血浆水平毫克/千克和10毫克/千克BZ。肌肉内注射5分钟后,血浆中BZ最高(暴露于2 mg / kg BZ的大鼠为154.6±22.3 ng / mL,暴露于10 mg / kg的大鼠为1024±269 ng / mL)。48小时后,未观察到BZ处于可检测水平。这种新方法可以在暴露观察到的生物后检测和定量生物样品中的BZ,并将进一步优化其他组织以观察BZ在器官中的分布。
更新日期:2020-01-10
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