[1]李　悦,贺志安,任方龙,等.人血清中拉莫三嗪浓度快速测定的高效液相色谱法[J].新乡医学院学报,2018,35(10):865-868.[doi:10.7683/xxyxyxb.2018.10.005]
　LI Yue,HE Zhi-an,REN Fang-long,et al.Determination of lamotrigine in human serum by high performance liquid chromatography[J].Journal of Xinxiang Medical University,2018,35(10):865-868.[doi:10.7683/xxyxyxb.2018.10.005]
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人血清中拉莫三嗪浓度快速测定的高效液相色谱法
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《新乡医学院学报》[ISSN:1004-7239/CN:41-1186/R]

卷:
35
期数:
2018年10
页码:
865-868
栏目:
基础研究
出版日期:
2018-10-05

文章信息/Info

Title:
Determination of lamotrigine in human serum by high performance liquid chromatography
作者:
李　悦1; 2; 3; 贺志安1; 2; 3; 任方龙2; 马淑君1; 2; 3; 任明芬4
（1.新乡医学院医学检验学院，河南　新乡　453003；2.新乡雅仕杰医学检验所质谱实验室，河南　新乡　453003；3.河南省免疫与靶向药物重点实验室，河南省分子诊断与医学检验技术协同创新中心，河南　新乡　453003；4.新乡医学院第二附属医院内科，河南　新乡　453002）
Author(s):
LI Yue1; 2; 3; HE Zhi-an1; 2; 3; REN Fang-long2; MA Shu-jun1; 2; 3; REN Ming-fen4
（1.School of Laboratory Medicine，Xinxiang Medical University，Xinxiang 453003；2.Mass Spectrometry Laboratory，Xinxiang Assegai Medical Laboratory Center，Xinxiang 453003；3.Henan Province Key Laboratory of Immunology and Targeted Trugs，Henan Province Collaborative Innovation Center of Molecular Diagnostics and Medicine Laboratory Technology，Xinxiang 453003；4.Department of Internal Medicine，the Second Affiliated Hospital of Xinxiang Medical University，Xinxiang 453002）
关键词:
高效液相色谱法; 拉莫三嗪; 血药浓度监测
Keywords:
high performance liquid chromatography; lamotrigine; therapeutic drug monitoring
分类号:
O657.7+2
DOI:
10.7683/xxyxyxb.2018.10.005
文献标志码:
A
摘要:
目的　建立简便快速测定人血清中拉莫三嗪（LTG）浓度的高效液相色谱法（HPLC）。方法　采用甲醇和乙酸铅沉淀蛋白法处理LTG血清样本，以苯代三聚氰胺为内标，波长为207 nm的二极管阵列检测器检测LTG的响应度，采用ES Industries Sonoma C18（2）色谱柱（50.0 mm×2.1 mm，3 μm）分离化合物，流动相A相为超纯水，B相为纯甲醇，体积分数20%甲醇洗脱，流速为0.6 mL·min-1，进样量20 μL，柱温40 ℃，建立检测LTG最适的液相条件及预处理方法，并依据《中国药典》2015年版通则中“生物样品定量分析方法验证指导原则”对所建方法的选择性、标准曲线、精密度与准确度、残留及稳定性进行验证。结果　LTG在1.18~37.75 mg·L-1范围内线性关系良好（r=0.999），在定量下限（1.18 mg·L-1）、低浓度（2.36 mg·L-1）、中浓度（18.88 mg·L-1）、高浓度（28.31 mg·L-1） LTG的批内与批间精密度的相对标准偏差均小于13.2%，准确度符合要求。经甲醇和乙酸铅沉淀蛋白法预处理过的LTG血清样本室温放置24 h后测定结果稳定，未经处理的血清样本于2~8 ℃冰箱存放1周后测定结果稳定。结论　建立了分析速度快、操作简便、选择性好、灵敏度高、符合生物样品分析要求的测定LTG临床血药浓度的HPLC分析方法。
Abstract:
Objective　To establish a simple and rapid high performance liquid chromatography（HPLC） for the determination of lamotrigine（LTG） concentration in human serum.Methods　The serum samples of LTG were performed by protein precipitation with methanol and lead acetate.The benzoguanamine was used as internal standard.The responsivity of LTG was detected with diode array detector at the 207 nm wavelength.Chromatographic separation was performed on a ES Industries Sonoma C18（2） column （50.0×2.1 mm，3 μm） using gradient elution.The mobile phase were methanol-water by volume fraction 20% methanol at a flow rate of 0.6 mL·min-1.The injection volume was 20 μL and the column temperature was maintained at 40 ℃.The most suitable liguid-phase conditions for determination of LTG concentration and pre-treatment methods were established.The established methods were verified according to "guidelines for the quantitative analysis of biological samples" in the general rules of the "Chinese pharmacopoeia（2015 edition）",including the selectivity,standard curve,precision and accuracy,residue and stability.Results　This method exhibited good linearity for LTG in the range of 1.18-37.75 mg·L-1（r=0.999）.The mean accuracy meet the requirement and the relative standard deviation in the quantitative lower limit，lower，medium and high concentration batch were below 13.2%.The results of the determination of LTG in pretreated serum samples were stable after placing at room temperature for 24 hours.The results of the determination of LTG in untreated serum samples were stable after storing at 2-8 ℃ in refrigerator for one week.Conclusion　A HPLC for the determination of LTG blood concentration is established and validated.The method has the advantages of fast analysis speed，simple operation，good selectivity，high sensitivity and meeting the requirements of biological sample analysis.

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更新日期/Last Update: 2018-10-05