LC-FAIMS-MS/MS for quantification of a peptide in plasma and evaluation of FAIMS global selectivity from plasma components.

As a continuation of the evaluation of the utility of high-field asymmetric waveform ion mobility spectrometry (FAIMS) in quantitative bioanalysis, we have developed a sensitive and selective method for the quantification of a peptide drug candidate in rat plasma using FAIMS coupled with liquid chromatography tandem mass spectrometry (LC-MS/MS). The LC-FAIMS-MS/MS method provided significant advantage over the corresponding LC-MS/MS method by reducing chemical/endogenous background noise associated with plasma matrix, thereby improving the sensitivity via increasing the signal-to-noise ratio. Linearity was established within 1-1000 nM in rat plasma, and the overall method accuracy and precision were good meeting the generally adopted acceptance criteria for a bioanalytical method. In a related investigation, we demonstrated the global selectivity of FAIMS from plasma endogenous components as a function of the compensation voltage (CV) across molecular masses that encompass small-molecule drugs. This work demonstrates that FAIMS coupled with LC-MS/MS can be highly advantageous in quantitative bioanalysis.