超高效液相色谱串联质谱法同时测定癫痫患儿拉考沙胺和吡仑帕奈血药浓度  

Simultaneous Determination of Blood Drug Concentrations of Lacosamide and Perampanel in Children with Epilepsy by UPLC-MS/MS

作　　者：林志燕[1] 杨宇[1] 苏妤萱 黄晓会[1] LIN Zhiyan;YANG Yu;SU Yuxuan;HUANG Xiaohui(Xinhua Hospital Affiliated to School of Medicine,Shanghai Jiao Tong University,Shanghai,China 200092)

机构地区：[1]上海交通大学医学院附属新华医院,上海200092

出　　处：《中国药业》2025年第9期53-57,共5页China Pharmaceuticals

基　　金：中国药理学会基金项目[CTDM(XM)-2018-02-002-038]。

摘　　要：目的建立同时测定人血清中拉考沙胺和吡仑帕奈血药浓度的超高效液相色谱串联质谱(UPLC-MS/MS)法,并用于癫痫患儿的血药浓度监测。方法色谱柱为AgilentSB-C_(18)柱(50 mm×2.1 mm,1.8μm),流动相为含0.1%甲酸的乙腈-水(梯度洗脱),流速为0.3 mL/min,柱温为40℃,进样量为1μL。以拉考沙胺-D6为拉考沙胺的内标,以吡仑帕奈杂质5为吡仑帕奈的内标。采用电喷雾离子源、多反应离子监测模式、正离子模式检测。结果该方法专属性良好,无内源性干扰,拉考沙胺和吡仑帕奈的质量浓度均在3.125~200 ng/mL范围内与待测物和内标峰面积的比值线性关系良好(R2>0.998);低、中、高质量浓度的回收率为91.39%~106.28%;日内精密度试验的RSD≤7.67%(n=5),日间精密度试验的RSD≤13.78%(n=5)。将该方法用于医院服用该药物的癫痫患儿的血药浓度监测,结果男性患儿的拉考沙胺血药浓度为(5.85±4.49)μg/mL,女性患儿为(6.47±3.98)μg/mL,男女性别间无显著差异(P>0.05);男性患儿的吡仑帕奈血药浓度为(572.52±340.77)ng/mL,女性患儿为(819.57±595.71)ng/mL,女性患儿显著高于男性患儿(P<0.05);较高年龄组(12~18岁)患儿的吡仑帕奈血药浓度较低年龄组(4~11岁)患儿低,但无显著差异(P=0.20)。结论该方法准确、快速、灵敏度高、操作简单,可用于拉考沙胺和吡仑帕奈的血药浓度监测。Objective To establish an ultra-high performance liquid chromatography-mass spectrometry(UPLC-MS/MS)method for simultaneous determination of the blood drug concentrations of lacosamide and perampanel in human serum,and to monitor the blood drug concentrations in children with epilepsy.Methods The chromatographic column was Agilent SB-C_(18) column(50 mm×2.1 mm,1.8µm),the mobile phase was acetonitrile(containing 0.1%formic acid)-water(gradient elution),the flow rate was 0.3 mL/min,the column temperature was 40℃,and the injection volume was 1µL.Lacosamide-D6 was taken as the internal standard of lacosamide,and impurity 5 of perampanel was taken as the internal standard of perampanel.The determination was performed by the electrospray ionization(ESI)source,multiple reactions monitoring(MRM)mode and positive ion mode.Results This method has good specificity and no endogenous interference.The linear ranges of lacosamide and perampanel were 3.125-200 ng/mL(R2>0.998).The recovery rates of low-,medium-,and high-mass concentrations of lacosamide and perampanel were in the range of 91.39%-106.28%.The intraday precision RSD was less than or equal to 7.67%(n=5),and the interday precision RSD was less than or equal to 13.78%(n=5).The method was applied to monitor the blood drug concentration of children with epilepsy taking the drug in the hospital,the results showed that the blood drug concentration of lacosamide in male children was(5.85±4.49)µg/mL,and that in female children was(6.47±3.98)µg/mL,without significant difference(P>0.05).The blood drug concentration of perampanel in male children was(572.52±340.77)ng/mL,which was significantly higher than(819.57±595.71)ng/mL in female children(P<0.05).The blood drug concentration of perampanel in the older age group(12-18 years old)was lower than that in the younger age group(4-11 years old),but there was no significant difference(P=0.20).Conclusion The method is accurate,rapid,highly sensitive,and simple,which can be used for monitoring the blood drug concentrations

关 键 词：超高效液相色谱串联质谱法 拉考沙胺 吡仑帕奈 癫痫患儿 血药浓度监测 

分 类 号：R917[医药卫生—药物分析学] R971.5[医药卫生—药学]