The application of liquid chromatography and capillary zone electrophoresis combined with atmospheric pressure ionisation mass spectrometry for the analysis of pharmaceutical compounds in biological fluids

HPLC coupled to atmospheric pressure ionisation mass spectrometry has almost replaced HPLC assays with UV, fluorescence, or electrochemical detection, due to its enhanced speed, sensitivity, and selectivity, especially when tandem-MS is used. To increase the speed and sensitivity of the drug assays further, high-speed HPLC, multi-component analysis, and mu HPLC are used on a routine basis. Sample preparation is recognized as an important issue in bioanalytics. The use of a 96-well plate format with automated liquid-handling systems, off-line and on-line solid-phase extraction or automated liquid-liquid extraction allows to cope with the high sample throughput enabled by LC-MS. Although LC-MS/MS represents the highest standard with respect to sensitivity and selectivity, LC-MS, as a less expensive alternative, is useful in many stages of drug discovery and development. CE-MS and CEC-MS appear to be an attractive alternative to HPLC-MS with respect to separation power, but both are a challenge in application and only seldomly used for the quantification of new drug candidates in biological fluids.