Characterization of drug permeability in Caco-2 monolayers by mass spectrometry on a membrane-based microfluidic device

In this study, an integrated microfluidic device was developed for drug permeability assays with real-time online detection by a directly coupled mass spectrometer. The integrated microfluidic device contained two independent channels sandwiched by a semipermeable polycarbonate membrane for cell culture, and micro solid-phase extraction (SPE) columns for sample clean-up and concentration prior to mass spectrometry detection. Curcumin, a model drug, was delivered to an upper or bottom channel by a pressure-driven flow to mimic dynamic in vivo conditions, and it was forced to permeate into the other side channel. The concentration of curcumin permeated with time was directly detected by an electrospray ionization quadrupole time-of-flight mass spectrometer (ESI-Q-TOF MS) with high sensitivity after micro-SPE pretreatment. The total analysis time only needed about 30 min, and only 6 mu L of the drug solution was required for each permeation experiment. The measured permeability of curcumin was consistent with the literature reported value. In addition, this technique offers the potential for parallelization and increasing throughput compared to conventional methods. Thus, the established platform provides a useful tool for drug permeability studies, which is crucial for drug discovery and development.