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拉莫三嗪是广谱抗癫痫药,常用于治疗简单部分性癫痫发作、复杂部分性癫痫发作.由于其治疗窗窄,体内药代动力学个体间差异较大,故临床上对拉莫三嗪进行常规血药浓度监测来指导合理用药.个体差异和联合用药会影响蛋白结合率,进一步影响拉莫三嗪游离药物浓度.与拉莫三嗪总血药浓度相比,游离血药浓度与不良反应和治疗效果之间的关系更为密切.因此,确定血浆中拉莫三嗪游离药物浓度对于临床治疗更有意义.本文使用超滤法提取血浆中游离的拉莫三嗪,采用高效液相色谱法(HPLC)进行游离浓度测定,并通过选择性、线性、定量下限、准确度、精密度、回收率和稳定性的研究对该方法进行验证.结果发现,拉莫三嗪游离浓度在0.20-10.0μg.mL-1◇=12.42×10-2c+ 5.47×10-3,r=0.9996),线性关系良好,最低定量下限为0.2 μg·mL-1.该方法日内、日间精密度(RSD)均＜15％,准确度为±4.69％;游离拉莫三嗪测定方法在三种不同浓度下的提取回收率均满足生物样品分析要求,并且在不同储存条件下拉莫三嗪稳定性良好.该方法简便、快速、灵敏度高,适用于临床游离血药浓度监测.“,”Lamotrigine (LTG) is a widely used antiepileptic drug (AED) for the treatment of new-onset,as well as refractory epilepsy.Due to the narrow treatment window and large individual variability in the pharmacokinetics and pharmacodynamics of LTG,therapeutic drug monitoring (TDM) is necessary in clinical practice to guide dose adjustments.Individual differences and drug combinations can also affect protein binding rate,which further affects the unbound concentration of LTG.The unbound fraction is more closely related to adverse reactions and therapeutic efficacy than total concentration.Therefore,it may be more meaningful to determine the unbound LTG concentration in plasma than the total concentration.Unbound LTG in plasma was extracted by ultrafiltration.High-performance liquid chromatography (HPLC) was used to measure unbound LTG concentration.This method was validated by studies of its selectivity,linearity,lower limit of quantification (LLOQ),accuracy,precision,recovery,and stability.The method was validated over a linear range of 0.2 to 10.0 μg.mL-1,and its LLOQ was 0.2 μg·mL-1.The method's relative standard deviations (RSDs) for intra-day and inter-day precision were less than 15％,and its accuracy (RE) was ±4.69％.The recoveries of unbound LTG at three different concentrations satisfied the requirements for the analysis of biological samples,and no significant degradation of LTG was observed under different storage conditions.A simple HPLC method showed good performance when used to measure unbound LTG concentration.This method might be used to study the relationship between unbound LTG concentrations and its effectiveness according to TDM.