Recently, we developed a novel microprobe electrospray ionization (μPESI) source and its coupled MS (μPESI-MS/MS) system. Here, we aimed to widely validate the μPESI-MS/MS method for quantitative analysis of drugs in plasma samples. Furthermore, the relationship between the quantitative performance of the μPESI-MS/MS method and the physicochemical properties of target drugs was analyzed. The μPESI-MS/MS methods for quantitative analysis of 5 representative drugs with a relatively wide range of molecular weight, pKa, and log P values were developed and validated. The results showed that the linearity, accuracy, and precision of these methods met the requirements of the European Medicines Agency (EMA) guidance. Then a total of 75 drugs from plasma samples were primarily detected using the μPESI-MS/MS methods, among which 48 drugs could be quantitatively measured. Logistics regression suggested that drugs with significantly greater log P and physiological charge had better quantitative performance using the μPESI-MS/MS method. Collectively, these results clearly demonstrate the practical application of the μPESI-MS/MS system as a rapid approach to the quantitative analysis of drugs in plasma samples.
Keywords: bioanalysis; micro probe electrospray ionization tandem mass spectrometry; probe electrospray ionization.