The application of past gradient capillary liquid chromatography mass spectrometry to the analysis of pharmaceuticals in biofluids

Fast gradient capillary high performance liquid chromatography (HPLC) coupl ed to a mass spectrometer has been successfully used for the analysis of ph armaceutical compounds from biological matrices, in the femtogram on column range, In the work reported in this paper, the use of capillary HPLC, on t he 180-mu m internal diameter scale, has shown a 30-fold improvement in det ection limits when compared to conventional 2-mm scale chromatography. The use of fast gradient elution resulted in a generic methodology which gave e xcellent chromatographic reproducibility and column longevity. This techniq ue has been used in conjunction with simple protein precipitation, with no deleterious effect on either the column life or the chromatographic perform ance. The use of capillary HPLC in bioanalysis has the potential to give a significant increase in assay sensitivity with the equipment currently in u se. In this paper the authors also present a modification to the current PE -Sciex ion-spray source which allows excellent spray adjustment in three di mensional accessibility, which is important when working with low flow rate s, as well as reducing the inherent system dead volume. Copyright (C) 1999 John Wiley & Sons, Ltd.