同位素稀释-高效液相色谱-质谱联用技术检测大鼠血浆中的芥子气水解产物

引用本文: 李春正, 陈佳, 钟玉环, 钟玉绪, 谢剑炜, 李桦. 同位素稀释-高效液相色谱-质谱联用技术检测大鼠血浆中的芥子气水解产物[J]. 分析化学, 2012, 40(10): 1567-1572. doi: 10.3724/SP.J.1096.2012.20249 shu

Citation: LI Chun-Zheng, CHEN Jia, ZHONG Yu-Huan, ZHONG Yu-Xu, XIE Jian-Wei, LI Hua. Simultaneous Quantification of Thioglycol and Thioglycol Sulfoxide in Rat Plasma by Isotope Dilution-Liquid Chromatography Tandem Mass Spectrometry[J]. Chinese Journal of Analytical Chemistry, 2012, 40(10): 1567-1572. doi: 10.3724/SP.J.1096.2012.20249 shu

同位素稀释-高效液相色谱-质谱联用技术检测大鼠血浆中的芥子气水解产物

通讯作者: 李桦

基金项目:
本工作系国家"重大新药创制"科技重大专项(2008ZXJ09006-001,2010ZXJ0900X-003-002)资助 (2008ZXJ09006-001,2010ZXJ0900X-003-002)

摘要: 应用同位素稀释-高效液相色谱-质谱联用技术(LC-MS/MS),建立了同时定量检测血浆中芥子气水解代谢产物硫二甘醇(TDG)和二羟乙基亚砜(TDGO)的方法。应用甲醇和乙腈混合溶剂沉淀染毒大鼠血浆中蛋白,采用 ZORBAX-C₁₈色谱柱(100 mm×3.0 mm, 3.5 μm),以5 mmol/L甲酸铵-甲醇梯度洗脱分离待测物。以d₈-TDG为内标,在正离子多反应监测模式下定性和定量分析TDG和TDGO。方法学验证结果表明,TDG在5-800 μg/L和TDGO在0.5-80.0 μg/L范围内均呈良好的线性关系(r²＞0.991),定量限分别为5和0.5 μg/L,加标回收率在101%-118%之间,方法的日内和日间精密度(RSD)均小于10%。对SD大鼠(n＝6)采用皮下注射方式进行染毒后采样测定,代谢动力学参数计算结果显示,TDG和TDGO的达峰时间(t_max)分别为30和60 min,峰值浓度(c_max)为(1724±227) μg/L和(301±115) μg/L,血浆浓度-时间曲线下面积(AUC)为(3286±249) μg·h/L和(1010±363) μg·h/L。

关键词:

English

Simultaneous Quantification of Thioglycol and Thioglycol Sulfoxide in Rat Plasma by Isotope Dilution-Liquid Chromatography Tandem Mass Spectrometry

1.
Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China

Corresponding author: 李桦

Received Date: 12 March 2012
Fund Project:
本工作系国家"重大新药创制"科技重大专项(2008ZXJ09006-001,2010ZXJ0900X-003-002)资助

Abstract: A method based on isotope dilution-liquid chromatography tandem mass spectrometry (HPLC-MS/MS) was developed and validated to simultaneously quantify metabolites of sulfur mustard, thioglycol (TDG) and thioglycol sulfoxide (TDGO), in rat plasma. Plasma samples were pretreated with the mixed solvent of methanol and acetonitrile to precipitate proteins. The separation of TDG and TDGO was achieved on a ZORBAX-C₁₈ column (3.0 mm×100 mm, 3.5 μm) by gradient elution with mobile phase consisting of methanol and 5 mmol/L ammonium formate aqueous solution. The mass spectrometric identification and quantification were performed using positive electrospray ionization and multiple reactions monitoring mode. An isotopic labeled TDG (d₈-TDG) was used as internal standard. The calibration curves for TDG and TDGO were linear (R²＞0.991) over the range from 5-800 μg/L, and 0.5-80 μg/L, with the lower limit of quantification at 5 and 0.5 μg/L. The recovery of the analytes ranged from 101% to 118%. The intra- and inter-day precisions (RSD) were all within 10%. The plasma was collected and analyzed from HD-exposure rats after subcutaneous administration, and the kinetics parameters of TDG and TDGO were calculated and demonstrated as follow: t_max 30 min and 60 min, c_max (1724±227) μg/L and (301±115) μg/L, AUC (3286±249) μg·h/L and (1010±363) μg·h/L, respectively.

Key words:

Sulfur mustard
/ Thioglycol
/ Thioglycol sulfoxide
/ Liquid chromatography-tandem mass spectrometry
/ Plasma
/ Toxicokinetics

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1.
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同位素稀释-高效液相色谱-质谱联用技术检测大鼠血浆中的芥子气水解产物

通讯作者: 李桦

English

Simultaneous Quantification of Thioglycol and Thioglycol Sulfoxide in Rat Plasma by Isotope Dilution-Liquid Chromatography Tandem Mass Spectrometry

Corresponding author: 李桦

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

同位素稀释-高效液相色谱-质谱联用技术检测大鼠血浆中的芥子气水解产物

通讯作者: 李桦

English

Simultaneous Quantification of Thioglycol and Thioglycol Sulfoxide in Rat Plasma by Isotope Dilution-Liquid Chromatography Tandem Mass Spectrometry

Corresponding author: 李桦

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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