Use of 'dilute-and-shoot' liquid chromatography-high resolution mass spectrometry in preclinical research: application to a DMPK study of perhexiline in mouse plasma.

摘要: This work describes a simple, sensitive and rapid liquid chromatography-high resolution mass spectrometry method for the quantitation of perhexiline simultaneous detection metabolites in C57bl/6 mice plasma. Only 5 μL plasma was used analysis. Pretreatment limited to 100-fold dilution ('dilute-and-shoot'). The analyte detected by high (Orbitrap™ technology). Three scan events were performed over entire chromatogram. Targeted single ion monitoring with data dependent acquisition employed confirmation, while full perform untargeted phase I II circulating metabolites. calibration curve linear (r(2)=0.990) ranging from 0.305 ng/mL (LLOQ) 10000 ng/mL. Matrix effect 6.1%. applied pharmacokinetic study mouse results obtained compared standard sample preparation based on protein precipitation chromatography-tandem (MRM mode) detection. new approach provided comparable terms pharmacokinetics parameters estimate sensitivity, additional information low consumption biological sample. combination 'dilute-and-shoot' together HRMS targeted represents suitable alternative classic bioanalytical approaches preclinical research.