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目的 建立用于人血清中拉考沙胺浓度测定的超高效液相色谱法(UPLC)，并应用于癫痫患儿拉考沙胺的治疗药物监测(TDM)。方法 血浆样本经7%高氯酸溶液预处理后，取上清液20μL直接进样行UPLC分析。以ACQUITY UPLC BEH C18(50mm×2.1 mm,1.7μm)为色谱柱，0.1%甲酸溶液-乙腈(85∶15)为流动相，流速0.2 mL·min-1，柱温40℃，检测波长265 nm，并对方法的专属性、标准曲线、回收率、精密度和稳定性进行考察。收集利用UPLC法进行拉考沙胺TDM的癫痫患儿158例，回顾性分析血药浓度监测结果。结果 拉考沙胺血清浓度在0.5～50.0μg·mL-1内线性关系良好(r2 > 0.999 6),检测限为0.5μg·mL-1，提取回收率为96.9%～103.7%，日内精密度RSD≤7.63%，日间精密度RSD≤8.22%，稳定性试验RSD≤14.85%。TDM结果显示拉考沙胺血清谷浓度为1.3～25.6μg·mL-1，其中<2.0μg·mL-1的患儿有49例(占31.01%),2.0～10.0μg·mL-1之间的有90例(占56.96%),> 10.0μg·mL-1的有19例(占12.03%)。结论 该研究建立的用于测定拉考沙胺血清浓度的UPLC法具有简便、快速、灵敏等优点，可用于癫痫患儿的拉考沙胺TDM。
Abstract：AIM To establish an ultra-high performance liquid chromatography(UPLC) for lacosamide quantification in human serum and to apply the approach for therapeutic drug monitoring(TDM) in pediatric patients with epilepsy. METHODS After the plasma samples were pretreated with 7% perchloric acid solution, 20 μL of the supernatant was directly analyzed by the UPLC. The separation was carried out on an ACQUITY UPLC BEH C18(50 mm×2.1 mm, 1.7 μm) column, with 0.1% formic acid-acetonitrile(85:15) as the mobile phase, at a flow rate of 0.2 mL·min-1, and a column temperature of 40℃, with a detection wavelength of 265 nm. The method specificity, standard curve, recovery, precision and stability were investigated. A total of 158 pediatric patients with epilepsy who underwent TDM of lacosamide using the UPLC were collected and analyzed for monitoring results. RESULTS The serum concentration of lacosamide was linear within 0.5-50.0 μg·mL-1(r2 > 0.999 6), and the limit of detection was 0.5 μg·mL-1. The recovery rates for extraction varied between 96.9% and 103.7%. The relative standard deviation(RSD) of intra-day precision was under 7.63%, while the inter-day precision was below 8.22%. Additionally, the RSD of stability test showed results of less than 14.85%. Results of the TDM indicated that the trough concentrations of lacosamide in the serum ranged from 1.3 μg·mL-1 to 25.6 μg·mL-1. Among the pediatric patients studied, 49 patients(31.01%) had concentrations lower than 2.0 μg·mL-1, 90 patients(56.96%) had concentrations between 2.0 μg·mL-1 and 10.0 μg·mL-1, and 19 patients(12.03%) had concentrations greater than 10.0 μg·mL-1. CONCLUSION The UPLC developed in the study for lacosamide quantification in serum has the advantages of simplicity, rapidity and sensitivity, and could be used for TDM of lacosamide in pediatric patients with epilepsy.
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基本信息:
DOI：10.19577/j.1007-4406.2025.06.009
中图分类号:R969
引用信息:
[1]李惠英,黎林波,李发双,等.UPLC测定拉考沙胺血药浓度的建立及其在癫痫患儿中的应用[J].中国临床药学杂志,2025,34(06):454-458.DOI:10.19577/j.1007-4406.2025.06.009.
基金信息:
云南省科技厅科技计划项目（编号202301AY070001-280）; 云南省卫生科技成果转化项目（编号YX-2023-02）