An automated online column extraction coupled with high-performance liquid chromatography (HPLC) and equipped with a double-trap column system was developed to determine valproic acid in human plasma without derivatization for routine therapeutic drug monitoring (TDM). 300 μL of plasma sample pretreated by precipitating the protein was injected into a Diamonsil C₁₈ extraction column in the first focusing step. After the elution of the pretreated sample, the targets were transferred from the extraction column to a strong cation exchange trap column through “central cutting” mode in the second focusing step. Finally, the targets were transferred from the strong cation exchange trap column to reverse-phase C₁₈ analytical column and were detected under an UV wavelength of 215 nm. In this method, the extraction system performs the sample injection, extraction, and transfer of targets from the extraction column to one trap column. Meanwhile, the analytical system performs the transfer of targets from other trap column to the analytical column, separation, and detection of targets. This method showed good linearity of calibration curve (R = 0.9999), precision (relative standard deviation (RSD) < 5.4%), and accuracy (within 5.6% in terms of relative error). Therefore, a promising approach was developed for routine monitoring of valproic acid concentration in human plasma.

开发了一种自动在线柱萃取结合高效液相色谱 (HPLC) 并配备双阱柱系统，用于测定人血浆中的丙戊酸，无需衍生化，用于常规治疗药物监测 (TDM)。在第一个聚焦步骤中，将通过沉淀蛋白质预处理的 300 μL 血浆样品注射到 Diamonsil C ₁₈提取柱中。预处理样品洗脱后，在第二个聚焦步骤中，通过“中心切割”模式将目标物从萃取柱转移到强阳离子交换捕集柱。最后，目标从强阳离子交换捕集柱转移到反相 C ₁₈分析柱，并在 215 nm 的紫外波长下检测。在该方法中，萃取系统执行样品注射、萃取和目标从萃取柱到一个捕集柱的转移。同时，分析系统执行目标从其他捕集柱到分析柱的转移、目标的分离和检测。该方法显示出良好的校准曲线线性（R  = 0.9999）、精密度（相对标准偏差 (RSD) < 5.4%）和准确度（相对误差在 5.6% 以内）。因此，开发了一种用于常规监测人血浆中丙戊酸浓度的有前途的方法。