Determination of lamotrigine in human plasma using liquid chromatography-tandem mass spectrometry
Determination of lamotrigine in human plasma using liquid chromatography-tandem mass spectrometry
复制标题
液相色谱-串联质谱法测定人血浆中拉莫三嗪的含量
DOI：
10.1002/npr2.12045
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发表时间：
2019
影响因子：
2.5
通讯作者：
Kitaichi Kiyoyuki
中科院分区：
文献类型：
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作者：
Itabashi Shogo;Bito Rina;Nishina Maika;Fukumoto Maki;Soda Midori;Doi Mitsunori;Usui Shigeyuki;Kitaichi Kiyoyuki
aimlamotriine （LTG）是一种广泛使用的抗癫痫药物，用于避免癫痫发作和维持无癫痫发作状态。然而，据报道，几个因素导致血浆LTG水平的个体差异，并且LTG的治疗目标范围因人而异。因此，为了优化LTG的有效剂量，我们开发了一种快速简便的测定血浆LTG浓度的方法。方法采用固相萃取法从人血浆中提取三嗪和内标罂粟碱。过滤后，将最终样品5 μL等分注入液相色谱串联质谱仪，用Cadenza CD - C18色谱柱（100 × 2mm, 3 μm）， 0.1%甲酸水溶液/乙腈（2/1,v/v）分离LTG和内标物。结果校准曲线在0.2 ~ 5.0 μg/mL范围内呈良好的线性关系，回收率、日内、日间精密度和准确度、基质效应、冻融稳定性和长期稳定性评价均具有良好的重复性。LTG和内标的保留时间分别为1.6 min和2.0 min，每个样品的总运行时间为3.5 min。结论建立了一种快速、简便的测定血浆LTG浓度的方法。目前的新系统可用于通知个体患者的LTG剂量调整。
AimLamotrigine (LTG) is a widely used anti‐epileptic drug that is administered to avoid seizures and to maintain seizure‐free status. However, several factors reportedly cause individual differences of plasma LTG levels, and the therapeutic target range of LTG varies between individuals. Thus, to optimize effective doses of LTG, we developed a rapid and simple method for determining plasma LTG concentrations.MethodsLamotrigine and the internal standard papaverine were extracted from human plasma using solid‐phase extraction. After filtration, 5‐μL aliquots of final samples were injected into the liquid chromatography‐tandem mass spectrometry instrument and LTG and internal standard were separated using a Cadenza CD‐C18 column (100 × 2 mm, 3 μm) with 0.1% formic acid in water/acetonitrile (2/1, v/v).ResultsThe calibration curve was linear from 0.2 to 5.0 μg/mL, and assessments of recovery, intra‐ and inter‐day precision and accuracy, matrix effects, freeze and thaw stability, and long‐term stability demonstrated good reproducibility. Retention times of LTG and internal standard were 1.6 and 2.0 minutes, respectively, and the total run time was 3.5 minutes for each sample.ConclusionWe developed a rapid and simple method for determining plasma LTG concentrations. The present novel system could be used to inform LTG dose adjustments for individual patients.