癫痫患者拉莫三嗪血药浓度的测定及临床分析

发布时间：2019-03-12 09:06

【摘要】：目的建立一种高效液相色谱分析方法，检测癫痫患者拉莫三嗪（Lamotrigine，LTG）血药浓度，结合检测结果探讨拉莫三嗪血药浓度与疗效及剂量的关系。方法利用高效液相（high performance liquid chromatographic，HPLC）建立并验证拉莫三嗪血药浓度分析方法。以替硝唑为内标，以氯仿作为萃取溶剂，流动相为乙腈-0.02mol/LKH2PO4（体积比为25:75），经Symmetry-C18WATO54275(250mm×4.6mm,5μ m)色谱柱洗脱、分离，柱温为室温，流速为1.0mL min-1，检测波长为210nm。应用以上色谱条件检测患者LTG血药浓度，依据测得LTG血药浓度将60例患者分为偏低浓度(1μg/mL4例)、有效浓度（1~8μg/mL49例）及偏高浓度（8μg/mL7例）3组，结果采用SPSS16.0统计软件进行分析。结果拉莫三嗪血药浓度在1~8μg/mL范围内线性关系良好（r=0.9998），最低检测限为0.5μg/mL，提取回收率在66.6-70.0%，日内、日间精密度均6.93%。60例患者中有49例患者LTG血药浓度在1~8μg/mL范围内，其中有43例LTG服用剂量为50mg~200mg；血药浓度在1~8μg/mL时，LTG治疗癫痫疗效良好，对全面性发作与部分性发作有效率有显著差异(P0.05)。结论所建立的高效液相色谱法操作简便，灵敏度高，经济廉价，适用于常规临床LTG血药浓度监测及药代动力学研究。LTG对多种癫痫类型有效，给药剂量在50mg~200mg范围内时，多数患者血药浓度可达到有效治疗浓度，，即1~8μg/mL，LTG对全面性发作疗效更佳。
[Abstract]:Aim to establish a high performance liquid chromatography (HPLC) method for the determination of lamotriazine (Lamotrigine,LTG) in patients with epilepsy, and to explore the relationship between the concentration of lamotriazine and the therapeutic effect and dose. Methods HPLC (high performance liquid chromatographic,HPLC was used to establish and verify the method for the determination of lamotriazine in human plasma. Tinidazole was used as internal standard, chloroform was used as extraction solvent, acetonitrile-0.02mol/LKH2PO4 (volume ratio was 25:75) was used as mobile phase. The mobile phase was eluted on Symmetry-C18WATO54275 (250mm 脳 4.6 mm, 5 渭 m) column. The column temperature was room temperature and the flow rate was 1.0mL min-1,. The detection wavelength is 210 nm. According to the above chromatographic conditions, 60 patients were divided into three groups: low concentration (1 渭 g / mL4), effective concentration (1 ~ 8 渭 g / mL49) and high concentration (8 渭 g / mL7) according to the serum concentration of LTG. Results the results were analyzed by SPSS16.0 software. Results the calibration curve of lamotriazine was linear in the range of 1 ~ 8 渭 g / mL (r = 0.9998). The detection limit was 0.5 渭 g / mL, and the recovery was 66.6 渭 g / mL,. The inter-day precision was 6.93%. In 49 of the 60 patients, the serum LTG concentration was in the range of 1 ~ 8 渭 g / mL, and 43 of them took 50 mg / mL of LTG. When the plasma concentration was between 1 渭 g / mL and 8 渭 g / LTG, LTG had a good therapeutic effect on epilepsy, and there was a significant difference in the effective rate between comprehensive seizure and partial seizure (P0.05). Conclusion the established high performance liquid chromatography is simple, sensitive, economical and cheap. It is suitable for routine clinical LTG blood concentration monitoring and pharmacokinetic study. LTG is effective for many types of epilepsy, and the dosage of LTG is within the range of 50mg~200mg. The plasma concentration of 1 ~ 8 渭 g / mL,LTG in most of the patients was more effective than that of the control group (1 ~ 8 渭 g / mol) in the treatment of all-round seizure.
【学位授予单位】：宁夏医科大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R742.1

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