As is shown by the examples presented in this chapter, CE provides high-quality data that would be of interest to clinical and forensic drug toxicolo-gists. The obvious tests to be replaced by CE involve methodologies that are too expensive, inaccurate, and/or prone to interferences. Prime examples include applications that require enantiomeric resolution, methods that consume high amounts of organic solvents, and assays that lack specificity. Before widespread adoption of CE assays in clinical and forensic drug toxicology can occur, however, validation and the quality assurance aspects of CE based assays have to be addressed. This is especially important for assays that are used for screening and/or confirmation of the presence or absence of illicit, abused, and banned drugs in urine. Initially, data with quality control urines was collected and published (34-36,63). In this work, data produced by electrokinetic capillary assays were found to be in agreement with the results of other techniques. Despite these encouraging results, additional efforts in exploring the use of CE in the clinical and forensic areas needs to be continued. Of critical importance is that analysis of a large number of external quality control urines, e.g., those offered by Cardiff Bioanalytical Services (UKNEQAS for drugs of abuse, Cardiff, UK) or College of American Pathologists (CAP), should be undertaken.

Currently the use of optical detection is the most popular detection mode employed. UV absorbance in the single and multiwavelength formats as well as fluorescence and laser-induced fluorescence has been successfully used in a number of publications (Table 1). Also, based upon the commercial availability of benchtop instrumentation, the use of MS is currently increasing and soon will establish itself as the detection method of choice for confirmation testing. Thus far, electrochemical detection (77), which is highly sensitive and selective, has received only cursory evaluation for detection of drugs in urine. This is mostly due to the lack of commercial detectors. The use of amperometric detection, however, has recently been demonstrated for the analysis of urinary promethazine and thioridazine (78).

Analysis of illicit and abused urinary drugs and their metabolites by CE offers many attractive features. CE offers separation methods that are amenable to the analysis of ionic (CZE, MECC) and neutral (MECC) solutes, including compounds that are difficult to analyze by GC. Furthermore, CE provides extremely high efficiency, resolving power, and separation speed when compared to HPLC. CE is also complementary to existing analytical methods, such as HPLC, GC, and high-throughput, automated immuno- and photometric assays. CE methods performed in capillaries of 25-75 ^m ID are considered nanoscale separation techniques, the capillary and sample plug volumes being 0.1-5 ^L and 1-10 nL, respectively. Versatility, high efficiency, and the possibility of direct urine injection or minimal sample preparation are appealing features for clinical and forensic analysis. Although CE is appealing for routine clinical and forensic use, the limit of detection is somewhat not as good as that of other separation techniques (including HPLC). This often calls for either on-line or off-line preconcentration of analytes prior to analysis. Fortunately, electrophoretic techniques feature a unique concentration effect (inherent to electrophoretic mass transport and very rarely seen in other separation techniques), which can provide compensation for the lack of sensitivity. Having instrumentation with a single fused silica capillary (as was the case for all the data presented in this chapter), sample throughput is limited since analyses can only be performed in a sequential mode. Having multiple capillaries in parallel would allow increased sample throughput and/or to permit the simultaneous analysis of a urinary extract in different buffers (18). Alternatively, the use of microchips in the single or multilane formats would provide even faster analyses and thus the highest throughput.

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