Strategies to improve the sensitivity in capillary electrophoresis for theanalysis of drugs in biological fluids

Capillary electrophoresis (CE) is a useful method to quantify drugs in biol ogical fluids. However, especially for blood or plasma samples, the sensiti vity is not sufficient to quantify drugs and their metabolites as they ofte n need to be quantified in the lower mu g/L range. To overcome this limitat ion and to increase the sensitivity, two strategies are applied: first, to increase the amount of analyte added to the capillary and, second, to incre ase the sensitivity on the detector site. To improve the sensitivity on the detector site, alternative detection techniques to UV detection, e.g., las er-induced fluorescence detection (LIF) or mass spectroscopy (MS), can be a pplied. However, LIF detection can only be used for fluorescent analytes an d the current equipment for CE-MS coupling provides only small improvements in sensitivity compared to UV detection. The detection window for UV detec tion can be enhanced using capillaries with an extended light path (bubble cell) or Z-shaped capillaries. Sensitivity improvements up to a factor of 1 0 have been reported. Increasing the amount of analyte in the capillary can be done either by chromatographic or by electrokinetic methods. Chromatogr aphic methods such as on-capillary membrane preconcentration have been used for several analytes. However, no validated application has been reported to date. In contrast, several validated examples can be found in which elec trokinetic techniques like sample stacking have been applied to achieve lim its of quantification in the lower mu g/L range. In conclusion, to date, el ectrokinetic techniques such as field-amplified sample injection offer the most promising results in achieving a sufficient sensitivity to quantify dr ugs in biological fluids.