摘要
建立了超高效液相色谱-串联质谱同时测定血清中加巴喷丁、拉莫三嗪、普瑞巴林、拉考沙胺、左乙拉西坦、托吡酯、奥卡西平、氯硝西泮、丙戊酸钠、卡马西平、苯巴比妥、苯妥英钠12种抗癫痫药物的方法。将非那西丁和氯唑沙宗分别作为正离子和负离子模式下的内标物,血清经乙腈沉淀蛋白质后,取上清液进样分析。采用ACQUITY UPLC BEH C18柱分离,流动相为水和甲醇(均含10 mmol/L甲酸铵),流速为0.4 mL/min。采用电喷雾电离源,在多反应监测和正、负离子模式下分段进行扫描分析。结果表明,12种抗癫痫药物在各自范围内线性关系良好,相关系数均大于0.992,在3个添加水平下方法的加标回收率为90.80%~114.0%,批内精密度RSD≤13.2%,批间精密度RSD≤14.8%。该方法专属性强,灵敏度高,可用于12种抗癫痫药物临床血药浓度监测及药代动力学研究。
A sensitive,high-throughput method was established for the simultaneous determination of 12 antiepileptics in serum by ultra high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS).The antiepileptics were gabapentin,lamotrigine,pregabalin,lacosamide,levetiracetam,topiramate,oxcarbazepine,clonazepam,sodium valproate,carbamazepine,phenobarbital and phenytoin sodium.Phenacetin and chlorzoxazone were used as internal standards.The antiepileptics and internal standards were extracted from serum by protein precipitation using acetonitrile as the precipitant.Chromatographic separation was achieved on an ACQUITY UPLC BEH C18 column with a gradient mobile phase comprising 10 mmol/L ammonium formate aqueous solution and methanol(containing 10 mmol/L ammonium formate)at a flow rate of 0.4 mL/min.Detection was performed in multiple reaction monitoring mode with ion mode switching.The results showed good linear trends in their respective concentration ranges and the correlation coefficients(r2)were greater than 0.992.The spiked recoveries of the 12 antiepileptics in serum were 90.80%-114.0%at the three spiked levels.The intra-assay(n=6)and inter-assay(n=3)precisions were less than 13.2%and 14.8%,respectively.The method has high specificity and sensitivity,and it can be used for clinical blood concentration monitoring and pharmacokinetic studies of the 12 antiepileptics.
作者
代静
高乐虹
彭方达
于丽佳
王朝东
王玉平
丁春光
DAI Jing;GAO Lehong;PENG Fangda;YU Lijia;WANG Chaodong;WANG Yuping;DING Chunguang(National Center for Occupational Safety and Health, Beijing 102308, China;Xuanwu Hospital Capital Medical University, Beijing 100053, China)
出处
《色谱》
CAS
CSCD
北大核心
2020年第8期900-905,共6页
Chinese Journal of Chromatography
基金
国家安全生产监督管理总局关键技术项目(2017005)
国家重点研发计划(2017YFC0907702)。
关键词
超高效液相色谱-串联质谱
血药浓度
抗癫痫药物
血清
ultra high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)
blood drug concentration
antiepileptics
serum