A novel method for the characterization of drug metabolites was developed by integrating chip-based solid-phase extraction (SPE) with an online electrospray ionization quadrupole time-of-fight mass spectrometer (ESI-Q-TOF-MS). The integrated microfluidic device was composed of circular chambers for cell culture and straight microchannels with shrink ends to pack the solid-phase material for sample cleanup and concentration prior to mass analysis. By connecting the two separated microchannels with polyethylene tubes, drug metabolism studies related to functional units, including cell culture, metabolism generation, sample pretreatment, and detection, were all integrated into the microfluidic device. To verify the feasibility of a drug metabolism study on the microfluidic device, the metabolism of vitamin E in human lung epithelial A549 cells was studied. The metabolites were successfully detected by online ESI-Q-TOF-MS with high sensitivity and short analysis time (8 min). By integrating several parallel channels, the desalting and concentration process could be simultaneously achieved. The total sample pretreatment time only needed about 15 min, and solvent consumption could be reduced to less than 100 μL. All this demonstrated that the developed microfluidic device could be a potential useful tool for cellular drug metabolism research.

中文翻译：

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电喷雾电离四极杆飞行时间质谱仪进行微流控细胞培养和代谢检测

通过将基于芯片的固相萃取（SPE）与在线电喷雾电离四极杆飞行时间质谱仪（ESI-Q-TOF-MS）集成在一起，开发了一种表征药物代谢产物的新方法。集成的微流控设备由用于细胞培养的圆形腔室和带有收缩端的直型微通道组成，以填充固相材料，以便在质量分析之前进行样品净化和浓缩。通过将两个分开的微通道与聚乙烯管连接起来，与功能单元相关的药物代谢研究（包括细胞培养，代谢生成，样品预处理和检测）都整合到了微流体装置中。为了验证在微流控设备上进行药物代谢研究的可行性，研究了维生素E在人肺上皮A549细胞中的代谢。通过在线ESI-Q-TOF-MS成功地检测到了代谢物，具有高灵敏度和短分析时间（8分钟）。通过整合多个平行通道，可以同时实现脱盐和浓缩过程。样品的总预处理时间仅需约15分钟，并且溶剂消耗可以减少到少于100μL。所有这些表明，开发的微流体装置可能是细胞药物代谢研究的潜在有用工具。样品的总预处理时间仅需约15分钟，并且溶剂消耗可以减少到少于100μL。所有这些表明，开发的微流体装置可能是细胞药物代谢研究的潜在有用工具。样品的总预处理时间仅需约15分钟，并且溶剂消耗可以减少到少于100μL。所有这些表明，开发的微流体装置可能是细胞药物代谢研究的潜在有用工具。