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 intr avenous anesthesia (Promedol, tramadol, ketamine, diazepam, Thiopental, and phentanyl) and of their metabolites in blood and urine of surgical patient s by chromatography-mass spectrometry was considered. Artifacts due to the chromatographic 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 (CC) was e xamined. The degradation products of the test preparations responsible for the generation of false positive results were found. Phentanyl, Promedol, k etamine, tramadol, Thiopental, diazepam, and their metabolites excreted wit h urine in the free forms were determined in the whole blood and urine of s urgical patients. Bound forms of metabolites and the initial medicinal prep arations excreted as complexes with glucuronic acid and other acids were al so determined in urine. Metabolites and impurity substances in the intraven ous anesthetics with similar mass spectra and retention times were distingu ished. 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-chlor obenzophenon (a product of diazepam hydrolysis), norketamine-Promedol, and anhydrotramadol (a GC artifact)-ketamine. The cumulation of an impurity sub stance from the tramadol preparation, identified by us as epoxytramadol, in the body was examined.