title: The application of fast gradient capillary liquid chromatography/mass spectrometry to the analysis of pharmaceuticals in biofluids.
abstract: Fast gradient capillary high performance liquid chromatography (HPLC) coupled to a mass spectrometer has been successfully used for the analysis of pharmaceutical compounds from biological matrices, in the femtogram on column range. In the work reported in this paper, the use of capillary HPLC, on the 180-micron internal diameter scale, has shown a 30-fold improvement in detection limits when compared to conventional 2-mm scale chromatography. The use of fast gradient elution resulted in a generic methodology which gave excellent chromatographic reproducibility and column longevity. This technique has been used in conjunction with simple protein precipitation, with no deleterious effect on either the column life or the chromatographic performance. The use of capillary HPLC in bioanalysis has the potential to give a significant increase in assay sensitivity with the equipment currently in use. In this paper the authors also present a modification to the current PE-Sciex ion-spray source which allows excellent spray adjustment in three dimensional accessibility, which is important when working with low flow rates, as well as reducing the inherent system dead volume.
authors.affiliation: International Development BioMet, Glaxo Wellcome Research and Development, Ware, Herts, UK.
authors.forename: R S
authors.initials: RS
authors.lastname: Plumb
authors.forename: G J
authors.initials: GJ
authors.lastname: Dear
authors.forename: D
authors.initials: D
authors.lastname: Mallett
authors.forename: I J
authors.initials: IJ
authors.lastname: Fraser
authors.forename: J
authors.initials: J
authors.lastname: Ayrton
authors.forename: C
authors.initials: C
authors.lastname: Ioannou
mesh_terms: D001826:Body Fluids / Q000737:chemistry; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D013058:Mass Spectrometry; D004364:Pharmaceutical Preparations / Q000032:analysis*; D015203:Reproducibility of Results
chemical_list: D004364:Pharmaceutical Preparations