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In drug analysis, GC/MS is used either to increase confidence in the identification of an unknown compound or to improve the limits of detection or quantitation through increased analytical specificity. Because of this unique combination of identification and quantitation capabilities, GC/MS methods, particularly confirmation methods, require a specific set of criteria for validation of methods and for performance verification in routine analysis.

There are two broad classes of drug analysis performed with GC/MS instrumentation. For some compounds, quantitative concentration thresholds have been established, on scientific and administrative grounds, to determine the presence of the drug or drug metabolite. When the threshold concentration, threshold ratio of amounts, or other defined parameter is exceeded, the compound is deemed to be present or to be present in nonphysiological amounts. In these cases, the performance of the method and instrument at the threshold has particular importance. The best-known example of the threshold approach was the development of specific administrative threshold concentrations and criteria for identification of five drugs of abuse for the federal drug-testing program.¹ For some other drugs or drug metabolites, however, detection at any documentable concentration is of concern. For these nonthreshold compounds, performance criteria for identification may be more important than the ability to quantify.

Although bench top GC/MS instrumentation has become more available and easier to use, a uniform practice must be established and maintained to provide acceptable evidence in an administrative appeal hearing or legal setting. Continuing improvements in theory and instrumentation will facilitate the use of new techniques, such as GC/MS/MS, in routine analysis. Thus, there is a need to define uniform practices not only for routine GC/MS methods, but also for the application of these more sophisticated approaches.