Itabashi Shogo, Bito Rina, Nishina Maika, Fukumoto Maki, Soda Midori, Doi Mitsunori, Usui Shigeyuki, Kitaichi Kiyoyuki
Laboratory of Pharmaceutics, Department of Biomedical Pharmaceutics, Gifu Pharmaceutical University, Gifu, Japan.
Department of Pharmacy, Wakayama Medical University Hospital, Wakayama, Japan.
Neuropsychopharmacol Rep. 2019 Mar;39(1):48-55. doi: 10.1002/npr2.12045. Epub 2019 Jan 2.
Lamotrigine (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.
Lamotrigine 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).
The 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.
We 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.
拉莫三嗪(LTG)是一种广泛使用的抗癫痫药物,用于预防癫痫发作并维持无癫痫发作状态。然而,据报道有几个因素导致血浆LTG水平存在个体差异,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方法来测定血浆LTG浓度。
采用固相萃取法从人血浆中提取拉莫三嗪和内标罂粟碱。过滤后,将5μL最终样品等分试样注入液相色谱 - 串联质谱仪,使用Cadenza CD - C18柱(100×2mm,3μm),以0.1%甲酸的水/乙腈溶液(2/1,v/v)分离LTG和内标。
校准曲线在0.2至5.0μg/mL范围内呈线性,回收率、日内和日间精密度与准确度、基质效应、冻融稳定性和长期稳定性评估均显示出良好的重现性。LTG和内标的保留时间分别为1.6分钟和2.0分钟,每个样品的总运行时间为3.5分钟。
我们开发了一种快速简便的方法来测定血浆LTG浓度。本新系统可用于指导个体患者的LTG剂量调整。