Artifacts in the determination of intravenous anesthetics by gas chromatography-mass spectrometry: Tramadol, the correlation between the structures of metabolites and impurity substances

The simultaneous determination of preparations used for multicomponent intravenous anesthesia (Promedol, tramadol, ketamine, diazepam, Thiopental, and phentanyl) and of their metabolites in blood and urine of surgical patients by chromatography-mass spectrometry was considered. Artifacts due to the Chromatographie interference of various preparations and their metabolites were revealed. The lability of the anesthetics and their metabolites in the course of sample preparation and analysis by gas chromatography (GC) was examined. The degradation products of the test preparations responsible for the generation of false positive results were found. Phentanyl, Promedol, ketamine, tramadol, Thiopental, diazepam, and their metabolites excreted with urine in the free forms were determined in the whole blood and urine of surgical patients. Bound forms of metabolites and the initial medicinal preparations excreted as complexes with glucuronic acid and other acids were also determined in urine. Metabolites and impurity substances in the intravenous anesthetics with similar mass spectra and retention times were distinguished. Methodological recommendations concerning the analysis of difficult-to-separate (by capillary gas chromatography) pairs of substances used for intravenous anesthesia and their metabolites are given. The following pairs of components are difficult to separate: Norpromedol-2-methylamino-5-chlorobenzophenon (a product of diazepam hydrolysis), norketamine-Promedol, and anhydrotramadol (a GC artifact)-ketamine. The cumulation of an impurity substance from the tramadol preparation, identified by us as epoxytramadol, in the body was examined.