Gas chromatography–mass spectrometry analysis of ketamine and its metabolites—A comparative study on the utilization of different derivatization groups

Method of chemical derivatization is the main difference among the GC–MS based methodologies reported for the analysis of ketamine and its major metabolites (norketamine and dehydronorketamine). These approaches included acylation and silylation resulting in the formation of acetyl, trifluoroacetyl, heptafluorobutyryl, and pentafluorobenzoyl (for acylation); and possibly trimethylsilyl and t-butyldimethylsilyl (for silylation) derivatives. This study evaluates the merits of these approaches based on the following criteria: reaction yields and ionization efficiency of the derivatization products; chromatographic characteristics; and cross-contributions to the intensities of ions designating the analyte and the internal standard. Pentafluorobenzoyl-derivatives were found to provide the best performance characteristics.