中国临床药理学杂志2026，Vol.42Issue(7)：982-989,8.DOI:10.13699/j.cnki.1001-6821.2026.07.013
同位素稀释-UPLC-MS检测血清和尿液中的14种镇静催眠药及代谢物
Determination of 14 sedative hypnotics and their metabolites in serum and urine by ultra-high performance liquid chromatography-tandem mass spectrometry with isotope dilution
摘要
Abstract
Objective To establish an ultra-high performance liquid chromatography-tandem mass spectrometry method for the determination of 14 sedative hypnotics and their metabolites in serum and urine.Methods Serum or urine samples were treated with acetonitrile to precipitate proteins.Separated on an Agilent EclipsePlus C18 RRHD column,the liquid was eluted with 0.1％formic acid in water and methanol,at a flow rate of 0.30 mL·min-1 and column temperature of 35℃.Quantified by the internal standard method,and multiple reaction monitoring(MRM)was performed by electrospray ionization(ESI+).The method was evaluated for specificity,standard curves and limits of quantification,precision and recovery,matrix effects,and stability.This method was applied to test the proficiency testing samples from the 2023 National Medical Emergency Toxicant Detection Laboratory Comparison Program,including qualitative and quantitative test samples for emergency poisoning assessment of sedative-hypnotic drugs in serum.Results The method demonstrated good specificity,with no cross-interference between the various sedative hypnotics and their metabolites.The linear range of 14 sedative hypnotics and metabolites were 1.00-45.00 μg·L-1,with a correlation coefficient greater than 0.998 2,the detection limit in serum and urine was 0.30 μg·L-1,and the quantification limit was 1.00 μg·L-1.In serum,recovery rates at three spiked levels(10.00,50.00 and 200.00 μg·L-1)ranged from 85.60％to 105.20％,with relative standard deviations(RSD)between 0.73％and 4.45％.In urine,recovery rates ranged from 88.93％to 108.12％,with relative standard deviations between 0.50％and 6.92％.Fluphenazine hydrochloride and clozapine were identified by this method.The two determined quantitative concentrations of fluphenazine hydrochloride were 339.00 μg·L-1 and 349.00 μg·L-1,with an average value of 344.00 μg·L-1 and a deviation of 2.90％.The two determined quantitative concentrations of clozapine were 1 668.00 μg·L-1 and 1 707.00 μg·L-1,with an average value of 1 688.00 μg·L-1 and a deviation of 2.30％.The final feedback result was satisfactory.Conclusion This method is rapid and accurate,making it suitable for emergency poisoning detection of sedative hypnotics.Its application to the blind sample detection of emergency poisoning cases is satisfactory.关键词
镇静催眠药/同位素内标/超高效液相色谱串联质谱/血清/尿液Key words
sedative hypnotics/isotope internal standard/ultra performance liquid chromatography-tandem mass spectrometry/serum/urine分类
医药卫生引用本文复制引用
孟春杨,吴玉田,周贻兵,林野,钟雪..同位素稀释-UPLC-MS检测血清和尿液中的14种镇静催眠药及代谢物[J].中国临床药理学杂志,2026,42(7):982-989,8.基金项目
贵州省卫生健康委科学技术基金资助项目(gzwkj2024-225) （gzwkj2024-225）
贵州省疾病预防控制中心新技术基金资助项目(2024-E-4技) （2024-E-4技）
