8种常见药(毒)物LC-MS/MS定性分析的保留时间和离子丰度比

目的探讨法医毒物分析中液相色谱-串联质谱(liquid chromatography-tandem mass spectrome⁃try,LC-MS/MS)法检测血液中毒品类(甲基苯丙胺、吗啡、氯胺酮)、苯二氮蓝卓类(艾司唑仑、咪达唑仑、地西泮、氯硝西泮)和巴比妥类(苯巴比妥)共3大类8种常见药(毒)物的保留时间和离子丰度比的最大允许偏差。方法在2根色谱柱、3种色谱条件下,经液液萃取后采用LC-MS/MS进行检测,分析质量浓度在检出限(limit of detection,LOD)、2倍检出限(2LOD)、定量限(limit of quantitation,LOQ)、1.5倍定量限(1.5LOQ)、2倍定量限(2LOQ)、4倍定量限(4LOQ)和6倍定量限(6LOQ)共7个较低质量浓度时保留时间和离子丰度比的偏差。结果血液添加样品中8种药(毒)物绝对保留时间的偏差在±0.05 min范围内的占98.11%,相对保留时间的偏差在±0.4%范围内的占96.21%。离子丰度比的最大偏差与质量浓度存在高度关联:药(毒)物质量浓度为LOQ及以上时,离子丰度比的绝对偏差和相对偏差都有95%以上分别在±25%和±40%范围内;质量浓度为LOQ以下时,范围可分别扩大至±35%和±50%。结论建议8种常见药(毒)物绝对保留时间的偏差判定范围为±0.1min,相对保留时间的偏差判定范围为±1.0%。质量浓度在LOQ及以上时离子丰度比的绝对偏差判定范围为±25%,相对偏差为±40%,质量浓度在LOQ以下时偏差判定范围可分别扩大至±35%和±50%。

Retention Time and Ion Abundance Ratio of 8 Common Drugs(Poisons)by LCMS/MS Qualitative Analysis

Objective To investigate the maximum allowable deviations of retention time and ion abundance ratio of the 8 common drugs(poisons)from 3 categories,poisons(methamphetamine,morphine,ketamine),benzodiazepines(estazolam,midazolam,diazepam,clonazepam)and barbiturates(phenobarbital)in blood,by liquid chromatography-tandem mass spectrometry(LC-MS/MS)in forensic toxicology analysis.Methods The deviations of retention time and ion abundance ratio at 7 low mass concentrations,limit of detection(LOD),2LOD,limit of quantitation(LOQ),1.5LOQ,2LOQ,4LOQ and 6LOQ,were tested by LC-MS/MS after liquid-liquid extraction under the conditions of two chromatographic columns and three chromatographs.Results The deviation of absolute retention time of 98.11%of 8 drugs(poisons)in the blood samples was within the range of±0.05 min,and that of the relative retention time of 96.21%was within the range of±0.4%.The maximum deviation of the ion abundance ratio was highly correlated with the mass concentration.When the mass concentration of drugs(poisons)was LOQ or above,more than 95%of the absolute deviation and relative deviation of the ion abundance ratio were in the range of±25%and±40%,respectively;when the mass concentration was below LOQ,the range could be expanded to±35%and±50%,respectively.Conclusion It is recommended for the determination range of the absolute retention time deviation of 8 common drugs(poisons)to be±0.1 min and that of the relative retention time deviation to be±1.0%.The determination range of absolute deviation of the ion abundance ratio should be±25%when the mass concentration is LOQ or above,and the relative deviation should be±40%.When the mass concentration is below LOQ,the deviation determination range can be expanded to±35%and±50%,respectively.