Improved GC/MS analysis of opiates with use of oxime-TMS derivatives

An improved gas chromatographic/mass spectrometric (GC/MS) assay is describ ed for the quantitation of codeine and morphine as trimethylsyl(TMS) deriva tives. The TMS derivatization of ketone-containing opiates results in the f ormation of multiple derivatives. Some of these products have retention tim es close to those of codeine-TMS and morphine-TMS. When the ketoopiates are present in samples assayed for codeine and morphine in urine, they can int erfere with the quantitation of these commonly targeted opiates. The assay was improved with the addition of a pre-BSTFA derivatization step, whereby hydroxylamine was used to convert the keto-opiates into the corresponding o xime derivative. These derivatives were then reacted with BSTFA to form the TMS ethers and TMS oxime derivatives. The oxime step enabled production of single derivatives for hydrocodone and hydromorphone. In addition, the ret ention times for the oxime-TMS derivatives were increased so that they no l onger elute near the targeted drugs of codeine and morphine. The addition o f the oxime step does not affect the sylation of codeine and morphine, and the accuracy and precision of this assay were unaffected.