Evaluation of various derivatization approaches for gas chromatography–mass spectrometry analysis of buprenorphine and norbuprenorphine

Various chemical derivatization approaches have been adapted for the analysis of buprenorphine and its major metabolite (norbuprenorphine) by GC–MS based methodologies. These approaches included alkylation, acylation, and silylation resulting in the formation of methyl, acetyl, trifluoroacetyl, pentafluoropropionyl, heptafluorobutyryl, and trimethylsilyl derivatives. This study conducted a comprehensive evaluation on 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 analytes and the internal standards. Under acidic derivatization conditions, the analytes could form three artifact products. Overall, derivatization by acetyl anhydride resulted in best performance characteristics.