拉莫三嗪血药浓度的测定及其在双相情感障碍患者中的应用

Determination of Lamotrigine Plasma Concentration and Its Application in Patients with Bipolar Depression

目的建立高效液相色谱-质谱联用法测定人血浆中拉莫三嗪血药浓度,并应用于临床。方法以拉莫三嗪同位素为内标,血浆样品经甲醇沉淀蛋白,采用Waters Cortecs C18色谱柱(2.1×50 mm,2.7μm)进行分离,以0.1%甲酸(v/v)水溶液和0.1%甲酸(v/v)甲醇溶液为流动相,流速0.4 ml/min。离子源采用正模式的电喷雾电离源(ESI+)操作,采用正离子多反应监测(MRM)方式进行检测。选取内蒙古精神卫生中心门诊及住院的36例双相情感障碍抑郁发作患者为研究对象。采用高效液相色谱-质谱联用法分别于基线及治疗后第2、第4周末测定患者拉莫三嗪血药浓度。同时采用汉密尔顿抑郁量表-24项(HAMD-24)和药物不良反应量表(TESS)来评估临床疗效和不良反应。结果血浆中拉莫三嗪检测方法的线性范围为0.0989~19.78μg/ml;最低检测可达到0.10μg/ml。日内、日间相对标准偏差(RSD)均小于3%,回收率均可达到85%。所测得的拉莫三嗪血药浓度与给药剂量差异有统计学意义(r=0.523,P<0.01),血药浓度与临床疗效差异无统计学意义(r=0.295、0.074,P>0.05)。结论本方法简便、快速、灵敏、重现性好,能够有效检测患者体内拉莫三嗪的血药浓度,且患者体内拉莫三嗪血药浓度与服药剂量呈相关性,能够为临床个体化用药提供依据。

Objective Establish a high performance liquid chromatography-mass spectrometry method for the determination of lamotrigine concentration in patients with bipolar disorder after taking lamotrigine and applied it to clinical practice.Methods Lamotrigine isotope was used as internal standard,and the plasma was achieved by protein precipitation using methanol.The analytes were performed using a Waters CortecsC18 column(2.1×50 mm,2.7μm)with 0.1% formic acid(v/v)aqueous solution and 0.1% formic acid(v/v)methanol solution as mobile phases at the flow rate of 0.4 ml/min.The ion source was detected by positive electrospray ionization source(ESI+)and positive ion multiple reaction monitoring(MRM).Thirty-six patients with bipolar depressive episode in Inner Mongolia Mental Health Center were selected as the study subjects.Plasma concentrations of lamotrigine were measured at baseline and at the 2nd and 4th weekend after treatment by high performance liquid chromatography-mass spectrometry.Clinical efficacy and adverse effects were evaluated using both the Hamilton Depression Scale 24-Item(HAMD-24)and the TESS Scale.Results The linear range of lamotrigine in plasma was 0.0989-19.78μg/ml.The Lowest detection limit is 0.10μg/ml.The relative standard deviations(RSDS)of both day and day were less than 3%,and the recoveries were up to 85%.The detected lamotrigine concentration was significantly correlated with the average daily dose(r=0.523,P<0.01).However,there was no significant difference between serum concentration and efficacy(r=0.295,0.074,P>0.05).Conclusion This method is simple,rapid,sensitive and reproducible.It can effectively detect the plasma concentration of lamotrigine in patients,and the plasma concentration of lamotrigine in patients is correlated with the dose of drug,which can provide a basis for clinical individualized medication.