FULLY-AUTOMATED SYSTEMATIC TOXICOLOGICAL ANALYSIS OF DRUGS, POISONS, AND METABOLITES IN WHOLE-BLOOD, URINE, AND PLASMA BY GAS-CHROMATOGRAPHY FULL SCAN MASS-SPECTROMETRY

The availability of automated, rapid and reliable methods for the syst ematic toxicological analysis (STA) of drugs and poisons in biosamples is of great importance in clinical and forensic toxicology laboratori es. Gas chromatography-continuous scan mass spectrometry (GC-MS) posse sses a high potential in STA because of its selectivity and identifica tion power. However, in order to develop a fully automated STA method based on GC-MS two main obstacles have to be overcome: (a) sample prep aration is rather sophisticated owing to the need to isolate analytes from the aqueous matrix and to allow a correct GC repartition of polar analytes; (b) the large amount of information collected within a sing le analysis makes it difficult to isolate relevant analytical informat ion (mass spectra of analytes) from the chemical noise. Using a bench- top GC-MS system equipped with a laboratory robot for sample preparati on (the Hewlett-Packard 7686 PrepStation) and an original method for m ass spectral purification, a fully automated STA procedure was develop ed involving isolation of drugs from the sample (whole blood with mini mal pretreatment, plasma, urine) by means of solid-phase extraction, d erivatization (trimethylsilylation) of the acidic-neutral and of the b asic extracts, GC-MS analysis, processing of data, and reporting of re sults. Each step of the procedure, and the method for data analysis in particular, can be easily integrated with other existing STA methods based on GC-MS. (C) 1998 Elsevier Science B.V. All rights reserved.