【摘要】 目的：建立血清拉莫三嗪治疗药物监测(TDM)方法和实验室质量控制体系。方法：以预冷冻的色谱纯乙腈为前处理试剂，采用高效液相色谱法(HPLC)建立血清拉莫三嗪浓度定量方法；基于方法学验证数据，建立Westgard多规则室内质量控制方案。采用自建HPLC法测定患者拉莫三嗪稳态谷浓度，并进行回顾性分析。参加国家卫生健康委员会临床检验中心室间质量评价，进一步评估该方法测定的准确性。结果：建立了适用于拉莫三嗪TDM的HPLC法，内源性物质、可能联合用药对拉莫三嗪的测定无干扰；该方法在1.00～64.00μg/mL线性关系良好(r~2>0.99),平均回收率(91.2%～95.8%)、精密度(批内RSD≤4.31%,批间RSD≤6.84%)、准确度(-6.70%≤RE≤4.34%)和稳定性均符合《中华人民共和国药典(四部)》(2020年版)“生物样品定量分析方法验证指导原则”的相关技术要求。三水平质控的西格玛值分别为4.07、4.12和4.07,推荐采用1-3s/2/3-2s/R-4s/3-1s多规则质控(n=3,r=1)作为该检测体系的室内质量控制规则。满分通过2024年度室间质量评价，确认该方法准确可靠。2024年3—10月，累计完成血清拉莫三嗪TDM 37例次，血药浓度达标率为70.27%(26例次)。结论：本研究为拉莫三嗪TDM方法和色谱分析法室内质量控制提供了方法学参考。更多还原

【Abstract】 OBJECTIVE: To establish the method for serum lamotrigine therapeutic drug monitoring(TDM) and laboratory quality control system. METHODS: Serum samples were pretreated with ice-cold acetonitrile for protein precipitation, and a quantitative method for determining serum lamotrigine concentration was established by using high performance liquid chromatography(HPLC). Westgard multi-rule internal quality control procedure was implemented based on methodological validation data. The self-developed HPLC method was used to determine the steady-state trough concentration of lamotrigine in patients and retrospective analysis was conducted. The reliability of the method was further assessed through the external quality assessment organized by the National Center for Clinical Laboratory. RESULTS: An HPLC method suitable for TDM of lamotrigine was established, showing no interference from endogenous substances or co-administered drugs. This method showed a good linear relationship within the range of 1.00 to 64.00 μg/mL(r~2>0.99). The average recovery rate(91.2%-95.8%), precision(intra-day RSD≤4.31%, inter-day RSD≤6.84%), accuracy(-6.70%≤RE≤4.34%), and stability all meet the technical requirements specified in the Guidelines for Validation of Quantitative Analysis Methods for Biological Samples of the 2020 edition of Chinese Pharmacopoeia: Part Ⅳ. Sigma metrics for three-level quality control were respectively 4.07, 4.12 and 4.07, supporting the adoption of the 1-3s/2/3-2s/R-4s/3-1s multi-rule protocol(n=3, r=1). The method received full scores in the 2024 external quality assessment. From Mar. to Oct.2024, 37 clinical TDM of lamotrigine were completed, and the compliance rate was 70.27%(26 cases). CONCLUSIONS: This study provides methodological reference for the internal quality control of lamotrigine TDM methods and chromatographic analysis methods.更多还原