De Silva Deepthika, Lee Steven, Duke Anna, Angalakurthi Siva, Chou Ching-En, Ebrahimpour Afshin, Thompson David E, Petrikovics Ilona
Department of Chemistry, Sam Houston State University, 1003 Bowers Blvd, Huntsville Texas, TX 77340, USA.
J Anal Methods Chem. 2016;2016:6546475. doi: 10.1155/2016/6546475. Epub 2016 Dec 7.
These studies represent the first report on the intravascular residence time determinations for the cyanide antidote dimethyl trisulfide (DMTS) in a rat model by using high performance liquid chromatography coupled with ultraviolet absorption spectroscopy (HPLC-UV). The newly developed sample preparation included liquid-liquid extraction by cyclohexanone. The calibration curves showed a linear response for DMTS concentrations between 0.010 and 0.30 mg/mL with = 0.9994. The limit of detection for DMTS via this extraction method was 0.010 mg/mL, and the limit of quantitation was 0.034 mg/mL. Thus this calibration curve provided a tool for determining DMTS in the range between 0.04 and 0.30 mg/mL. Rats were given 20 mg/kg DMTS dose (in 15% Polysorbate 80) intravenously, and blood samples were taken 15, 60, 90, 120, and 240 min after DMTS injections. The data points were plotted as DMTS concentration in RBCs versus time, and the intravascular residence time was determined graphically. The results indicated a half-life of 36 min in a rat model, suggesting that the circulation time is long enough to provide a reasonable time interval for cyanide antagonism.
这些研究首次报道了采用高效液相色谱-紫外吸收光谱法（HPLC-UV）在大鼠模型中测定氰化物解毒剂二甲基三硫醚（DMTS）的血管内停留时间。新开发的样品制备方法包括用环己酮进行液-液萃取。校准曲线显示，DMTS浓度在0.010至0.30mg/mL之间呈线性响应，相关系数R² = 0.9994。通过这种萃取方法测定DMTS的检测限为0.010mg/mL，定量限为0.034mg/mL。因此，该校准曲线为测定浓度在0.04至0.30mg/mL之间的DMTS提供了一种工具。给大鼠静脉注射20mg/kg DMTS剂量（溶于15%聚山梨酯80中），在注射DMTS后15、60、90、120和240分钟采集血样。将数据点绘制成红细胞中DMTS浓度与时间的关系图，并通过图形确定血管内停留时间。结果表明，在大鼠模型中半衰期为36分钟，这表明循环时间足够长，可为氰化物拮抗作用提供合理的时间间隔。
