UPLC-MS/MS法检测佐匹克隆及其在大鼠体内动态分布研究

Distribution of zopiclone by UPLC-MS/MS and its dynamic distribution in rats

目的建立安眠镇静药佐匹克隆的检测方法及其在大鼠体内动态分布模型。方法实验组大鼠用佐匹克隆橄榄油溶液(47.25mg/kg)灌胃给药,空白对照组大鼠采用橄榄油灌胃,分别于0.5、1、1.5、2.5、5、8、12h后采集心血后处死大鼠,分别取心、肝、肺、脾、肾、胃、大脑组织,采用超高效液相色谱-串联质谱法(UPLC-MS/MS)检测各组织中佐匹克隆的质量浓度。结果佐匹克隆与内标物SKF525A出峰时间分别为1.43、1.6min。各组织中佐匹克隆在5~5000ng/mL(g)线性关系良好。佐匹克隆在10、100、1000ng/mL三个浓度下日间、日内精密度良好,在各组织中平均萃取回收率高。灌胃给药后大鼠各组织中佐匹克隆含量在0.5~1h内呈上升趋势,在1h时达到峰值,在各时间点,佐匹克隆在胃壁组织中含量较其他组织高,心血和大脑组织中相对较少。结论本课题建立的UPLCMS/MS法动态检测大鼠各组织中佐匹克隆的含量具有高效性、可靠性的特点,这对今后法医学案件中涉及到佐匹克隆定性定量检验有一定的参考价值。

Objective To establish a model for the detection of zopiclone and its dynamic distribution in rats.Methods The experimental group were given zopiclone solution(47.25 mg/kg)by gavage,the control group were given olive oil.After 0.5,1,1.5,2.5,5,8 and 12 h of gavage,heart blood was collected,the heart,liver,lung,spleen,kidney,stomach and brain tissues were taken.The mass concentration of zopiclone in each tissue was determined by UPLC-MS/MS.Results The retention time of zopiclone and SKF525 A are 1.43 and 1.6 min respectively.Zopiclone content in all of tissues had a reliable linear relationship between 5~5,000 ng/mL(g).There are good intra-day precision and inter-day precision,with high average recovery rates at concentrations of zopiclone at three concentrations of 10,100 and 1,000 ng/mL.After gavage,zopiclone content in all of tissues showed an increasing trend within 0.5~1 h,and reached the peak at 1 h.Combined with the comparison of the same time point,zopiclone content in gastric wall tissues were higher than other tissues,while the concentrations in blood and brain tissues were relatively lower.Conclusion The UPLC-MS/MS has the characteristics of high efficiency and reliability for dynamic detection of zopiclone content in varous tissues of rats,which has certain reference value for the qualitative and quantitative determination of zopiclone in forensic cases.