High-sensitivity quantitation of cabergoline and pergolide using a triple-quadrupole mass spectrometer with enhanced mass-resolution capabilities

Quantitative analysis of pharmaceuticals with low systemic plasma levels requires the utmost in sensitivity and selectivity from the analytical method used. A recently introduced triple‐quadrupole mass spectrometer with unique enhanced mass‐resolution capability was evaluated in the analysis of two such drugs, cabergoline and pergolide, in plasma. Liquid chromatographic/electrospray ionization selected reaction monitoring determination of cabergoline in plasma at unit mass‐resolution demonstrated improved sensitivity (50 fg on‐column), coupled with suitable accuracy and precision over a broad linear dynamic range covering five orders of magnitude (50 fg to 5 ng on‐column). Liquid chromatographic/atmospheric pressure chemical ionization selective reaction monitoring determination of pergolide in plasma also attained a high level of sensitivity (500 fg on‐column) at unit mass‐resolution, with accuracy and precision values well within pharmaceutical industry standards. Again, a linear dynamic range covering five orders of magnitude (500 fg to 50 ng on‐column) was achieved for the assay. Utility of the enhanced mass‐resolution feature of the triple‐quadrupole mass spectrometer in the determination of pergolide resulted in an improvement in analyte sensitivity (250 fg on‐column) and linear dynamic range (250 fg to 50 ng on‐column). Copyright © 2003 John Wiley & Sons, Ltd.