Labor- and time-intensive sample preparation and liquid chromatography mass spectrometry (LC-MS) analysis are required for traditional pharmacokinetics (PK) studies. In order to simplify and accelerate the analytical process of the PK study, solid phase microextraction (SPME) combined with thermal desorption-electrospray ionization/mass spectrometry (TD-ESI/MS) was developed for rapid characterization of trace drug in biological fluids. Methylphenidate in plasma was extracted and concentrated by direct immersion SPME using fused-silica fibers coated with polydimethylsiloxane. The analytes on the SPME fiber were then characterized by TD-ESI/MS. Matrix-matched calibration with multiple reaction monitoring analysis was conducted to quantify methylphenidate. A linear calibration curve was constructed over a concentration range of 0.2–25 ng mL⁻¹ (r = 0.997). The quantitative results obtained by SPME-TD-ESI/MS were validated by LC-MS/MS. The average relative error for both methods was found to be −5.3%. As a viable alternative to LC-MS, SPME-TD-ESI/MS enables simple, rapid, and high-throughput analysis of drugs in plasma. The developed approach is particularly beneficial to PK studies for a very small sample volume (10 μL) is needed, the extraction time is as short as 3 min, and the detection time is less than 30 s.

传统药代动力学（PK）研究需要劳动和时间密集的样品制备和液相色谱质谱（LC-MS）分析。为了简化和加速PK研究的分析过程，开发了固相微萃取（SPME）结合热脱附-电喷雾电离/质谱（TD-ESI / MS）来快速表征生物流体中的痕量药物。提取血浆中的哌醋甲酯，并使用涂有聚二甲基硅氧烷的熔融石英纤维通过直接浸入SPME进行浓缩。然后通过TD-ESI / MS对SPME纤维上的分析物进行表征。用多反应监测分析进行基质匹配的校准以量化哌醋甲酯。在0.2–25 ng mL的浓度范围内绘制线性校准曲线^-1（r = 0.997）。通过LC-MS / MS验证了SPME-TD-ESI / MS获得的定量结果。两种方法的平均相对误差为-5.3％。作为LC-MS的可行替代品，SPME-TD-ESI / MS可以对血浆中的药物进行简单，快速和高通量的分析。对于需要非常小的样品量（10μL），提取时间短至3分钟且检测时间少于30 s的情况，开发的方法对PK研究特别有益。