A novel high-performance liquid chromatography-diode array detection method based on microextraction by packed sorbent (MEPS) as sample preparation approach is described for the determination of zonisamide (ZNS) in human plasma. MEPS parameters were optimised using a Plackett-Burman experimental design to achieve the best extraction conditions. The chromatographic separation of ZNS and chloramphenicol [internal standard (IS)] was achieved in less than 5 min on a C18-column, at 35 °C, using a mobile phase composed of acetonitrile/water (35:65, v/v) pumped isocratically at 1.0 mL min-1. ZNS and IS were detected at 240 nm. No endogenous and exogenous interferences were observed at the retention times of the analyte of interest (ZNS) and IS. A good linearity was obtained for ZNS (r2 = 0.9960) in the range of 0.2-80 µg mL-1 in plasma. The method was shown to be precise (CV ≤13.3%) and accurate (bias ±12.3%), and the absolute recovery ranged from 63.8% to 65.2%. The stability of ZNS was demonstrated in plasma samples in all predictable handling and storage conditions. The proposed assay was applied to the analysis of human plasma samples obtained from epilepsy patients under ZNS therapy and the results supported its usefulness for therapeutic drug monitoring in clinical practice.

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实验设计优化的装填吸附剂微萃取-HPLC测定人血浆中唑尼酰胺的新方法

介绍了一种基于填充吸附剂（MEPS）微萃取作为样品制备方法的高效液相色谱-二极管阵列检测方法，用于测定人血浆中的唑尼沙胺（ZNS）。使用Plackett-Burman实验设计优化了MEPS参数，以达到最佳提取条件。在35°C的C18色谱柱上，使用乙腈/水（35:65，v / v）组成的流动相，在不到5分钟的时间内完成了ZNS和氯霉素[内标（IS）]的色谱分离。以1.0 mL min-1等度泵取。在240nm处检测到ZNS和IS。在目标分析物（ZNS）和IS的保留时间未观察到内源性和外源性干扰。血浆中ZNS的线性良好（r2 = 0.9960），范围为0.2-80 µg mL-1。结果表明该方法准确（CV≤13.3％）和准确（偏差±12.3％），绝对回收率在63.8％至65.2％之间。在所有可预测的处理和储存条件下，血浆样品中ZNS的稳定性都得到了证明。拟议的测定方法用于ZNS治疗的癫痫患者的血浆样品的分析，结果支持了其在临床实践中对治疗性药物监测的实用性。