Pharmacokinetic investigations with direct injection of plasma samples: Possible savings using capillary electrophoresis (CE)

Capillary electrophoresis (CE) is often regarded as a separation technique of choice because of its high selectivity and its cost advantages compared to LC, RSD% of 0.5% have become standard for quality control assays. Using CE, sample pretreatment can often be significantly reduced, leading to nota ble savings of labor and regent costs. Moreover, errors from sample pretrea tment are avoided. A number of pharmaceuticals (e.g. acetaminophen, salicyl ic acid, sulfamethoxazole, theophylline, tolbutamide, and trimethoprim) hav e been determined in human plasma on underivatized fused silica capillaries by MEKC without sample pretreatment, the total analysis time being only 10 min. An sodium dodecyl sulfate-containing berate buffer (60 mM with 200 mM SDS) at pH 10 has been used. Between runs, proteins adsorbed to the capill ary wall are removed by a rinsing regimen consisting of SDS buffer and eith er acetonitrile (e.g. 50% v/v) or isopropanol (e.g. 10% v/v). Other rinsing approaches are discussed (salts, enzyme containing solutions, organic solv ents, sodium hydroxide, hydrofluoric acid). The separation system is tested in a concentration range between 10 ng/mL and 100 mu g/mL, the detection l imit being about 5 ng/mL. The sensitivity has been substantially improved c ompared to preceding work using field-amplified injection mechanisms and ef ficient computer algorithms that take advantage of multiwavelength detectio n. Correlations between the limit of quantitation (LOQ), the limit of detec tion (LOD) and the signal/noise ratio are discussed. A day-to-day precision for relative peak areas of 1 to 2% relsdv (n > 40) has been reached in the upper concentration range. Thus, not only drug monitoring but also pharmac okinetic investigations from blood plasma have become possible without furt her sample pretreatment.