HPLC法测定人血浆中拉莫三嗪的浓度及其影响因素研究

目的:建立测定人血浆中拉莫三嗪(LTG)浓度的方法,分析LTG血药浓度的相关影响因素。方法:血浆样品以甲醇处理后采用高效液相色谱(HPLC)法进行测定,其中内标为氯霉素,流动相为乙腈-磷酸盐缓冲液(30∶70),色谱柱为Luna C18,流速为1ml/min,检测波长为306 nm。对收集的病例进行分组,应用逐步回归法分析影响LTG血药浓度的各类因素;应用相关分析法分析不同组别中的影响因素。结果:拉莫三嗪的血药浓度在0.5²0.0μg/ml范围内线性关系良好(r=0.999 5),最低检测限为0.5μg/ml;低、中、高3种质量浓度的平均方法回收率分别为(94.39±1.57)%、(95.57±2.22)%、(91.81±2.11)%;LTG血药浓度与LTG给药剂量、联用丙戊酸(VPA)呈正相关(r分别为0.641 7、2.568 0,P<0.05),与联用苯巴比妥(PB)呈负相关(r=-2.048 2,P<0.05);性别、年龄及体质量与其不存在显著的相关关系(P>0.05)。结论:本试验建立的HPLC法操作简便、快捷、回收率高、精密度好,适用于临床上常规监测LTG的血药浓度;LTG血药浓度可受LTG给药剂量、联合应用VPA及PB等因素的影响,因此在临床有必要开展其血药浓度监测,实行个体化给药。

Determination of Lamotrigine Concentration in Human Plasma by HPLC and Study on Its Influencing Factors

OBJECTIVE： To establish a method for the determination of lamotrigine （LTG） concentration in human plasma, to analyze the influential factors of plasma concentration of LTG. METHODS.. After treated with methanol, the plasma sample was de termined by HPLC using chloramghenicol as internal standard. The determination was performed on Luna C8 column with mobile phase consisted of acetonitrilephosphate buffer （30：70） at the flow rate of lml/min. The detection wavelength was set at 306 rim. The collected cases were divided into groups, and stepwise regression method was used to analyze the influential factors of plasma concentration of LTG; correlation analysis method was adopted to investigate influential factors in different groups. RESULTS： The linear range of LTG were 0.520.0 μg/ml （r=0.999 5）, The lowest limit of detection was 0.5 μg/ml. Average recoveries were （94.39 ± 1.57）%, （95.57 ± 2.22）% and （91.81 ± 2.11）% at low, medium and high concentrations, respectively; plasma concentra tion of LTG had a positive correction with LTG dose （r0.641 7,P〈0.05） and comedication with VPA （r=2.568 0,P〈0.05） and a negative correction with the comedication with PB （r=2.048 2, P〈0.05） ; while there was no correction with the sex, age and weight （P〉0.05）. CONCLUSIONS： HPLC method is proved to be simple and rapid with high recovery and precision, and suitable for the plasma concentration monitoring of LTG. LTG dose, comedication with VPA or PB significantly influence plas ma concentration of LTG, therefore, it is necessary to carry out plasma concentration monitoring and implement individualized ad ministration.