title: LC-FAIMS-MS/MS for quantification of a peptide in plasma and evaluation of FAIMS global selectivity from plasma components.
abstract: 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.
authors.affiliation: Bioanalytical and Discovery Analytical Sciences, Bristol-Myers Squibb Company, Route 206 and Province Line Road, Princeton, New Jersey 08543, USA. yuan-qing.xia@bms.com
authors.forename: Yuan-Qing
authors.initials: YQ
authors.lastname: Xia
authors.forename: Steven T
authors.initials: ST
authors.lastname: Wu
authors.forename: Mohammed
authors.initials: M
authors.lastname: Jemal
mesh_terms: D000818:Animals; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods*; D008970:Molecular Weight; D010455:Peptides / Q000097:blood* / Q000737:chemistry* / Q000627:therapeutic use; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D010455:Peptides