人血浆6种中枢神经系统药物气相色谱-质谱法测定及临床应用

Simultaneous Determination of Six Central Nervous System Drugs in Human Plasma by GC-MS and Its Application

目的建立人血浆苯巴比妥、酰胺咪嗪、地西泮、硝西泮、艾司唑仑、阿普唑仑等药物的气相色谱-质谱(GC-MS)定性、定量分析方法,并用于指导中枢神经系统药物中毒的临床抢救。方法血浆样品经乙酸乙酯提取,以保留时间、特征离子和谱库检索为定性指标,咖啡因为内标,采用选择离子模式定量。结果酰胺咪嗪、地西泮、艾司唑仑、阿普唑仑在0.05～20.0mg·L-1内均呈良好线性关系,最低检出浓度为0.008mg·L-1。苯巴比妥、硝西泮在0.1～40.0mg·L-1内均呈良好线性关系,最低检出浓度为0.02mg·L-1。回收率为97.78%～109.32%,日内RSD<9.62%,日间RSD<9.70%。结论所建立方法系统性好,快速、准确,能准确测定血浆中苯巴比妥、酰胺咪嗪、地西泮、硝西泮、艾司唑仑、阿普唑仑等药物含量。

OBJECTIVE To establish an analytical method for determination of phenobarbital,carbamazepine,diazepam,nitrazepam,estazolam,alprazolam in human plasma by gas chromatograph-mass spectrometry（GC-MS） and apply to the diagnosis and treatment of central nervous system drug poisoning. METHODS The plasma sample was extracted with ethyl acetate,and compounds were identified by retention time,diagnostic ions and library searches. Six central nervous system drugs were analyzed by the selected-ion monitoring mode,and caffeine was used as the internal standard. RESULTS Carbamazepine,diazepam,estazolam,alprazolam showed good linearity （r≥0.997 6） in the rang of 0.05～20.0 mg·L-1,and the limit of quantitation was about 0.008 mg·L-1. Phenobarbital and nitrazepam showed good linearity （r≥0.997 5） in the rang of 0.1～40.0 mg·L-1,and the limit of quantitation was about 0.02 mg·L-1.The recoveries of 6 central nervous system drugs were in the range of 97.78%～109.32%.The RSDs within-day and between-day were less than 9.62% and 9.70%,respectively. CONCLUSION The method is rapid and accurate. It can be used to determine and screen 6 central nervous system drugs in human plasma.