Systematic toxicological analysis

The screening strategy for systematic toxicological analysis (STA) must be very extensive, because several thousands of drugs or pesticides should be considered. In STA the substance(s) present is (are) not known at the start of the analysis. In such a 

TABLE 16.1. Comparison of Order of Examination for Poison Groups, Target Specimens, and Methods Commonly Used in Systematic Toxicological Analysis 

Order Material Group of Compound Screening Method Sample Preparation Method 

1 Lungs, brain, blood Gases (carbon monoxide, cyanide) Direct-reading colorimetric indicator tubes Head-space Microdiffusion GC 

2 Blood, vitreous humor, urine Ethanol ADH enzymatic Spectrophotometric Head-space GC 

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Drummer OH. 1999. Chromatographic screening techniques in systematic toxicological analysis. J Chromatogr B 733 27. 

Muller, C., Schafer, P., Stortzel, M., Vogt, S., and Weinmann, W. (2002). Ion suppression effects in liquid chromatography-electrospray-ionization transport-region collision induced dissociation mass spectrometry with different serum extraction methods for systematic toxicological analysis with mass spectra libraries. /. Chromatogr. B 773, 47— 52. 

Tracqui A, Kintz P, Mangin P. Systematic toxicological analysis using HPLC/Dad. Journal of Forensic Sciences 40, 254-262, 1995. 

Maurer, H. H. Kraemer, T. Ledvinka, O. Schmitt, C. J. Weber, A. A. 1997. Gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) in toxicological analysis. Studies on the detection of clobenzorex and its metabolites within a systematic toxicological analysis procedure by GC-MS and by immunoassay and studies on the detection of alpha- and beta-amanitin in urine by atmospheric pressure ionization electrospray LC-MS. J. Chromatogr. B Biomed. Sci Appl., 689,81-89. 

R. A. de Zeeuw, J. P. Franke, and M. Bogusz, High performance liquid chromatography with a multichannel diode-array spectro-photometric detector in systematic toxicological analysis. In Analytical Methods in Forensic Chemistry (M. H. Ho, ed.), Ellis Horwood, New York, 1990, p. 212. 

Maurer HH, Bickeboeller-Friedrich J (2000) Screening procedure for detection of antidepressants of the selective serotonin reuptake inhibitor type and their metabolites in urine as part of a modified systematic toxicological analysis procedure using gas chromatography-mass spectrometry. J Anal Toxicol 24 340-347... 

Maurer HH (1992) Systematic toxicological analysis of drugs and their metabolites by gas chromatography-mass spectrometry. J Chromatogr 580(1—2) 3 11... 

Directions of Analysis Analytical procedures depends on the type of problem set. Unknown circumstances of an event or an unknown toxic factor require the application of systematic toxicological analysis (STA), so that the analytical procedure encompasses as many toxic substances as possible. In cases where the administered toxic compound is known, first of all a course of analysis targeted at this compound is conducted, and a positive result must be confirmed by another independent method. When working on a case in which only the symptoms of the action of an unknown toxic factor are given, the ability to use complementary techniques as well as knowledge of the fields of medicine, pharmacology and pharmacokinetics are of particular importance [53]. 

Systematic Toxicological Analysis The number of toxic compounds that must be taken into account in cases where the circumstances of an incident are completely unknown (e.g. a corpse found in a forest, an unconscious person found in a park) is continuously growing. It is not possible to encompass all the various chemical compounds that are significant from a toxicological point of view in one analytical process. 

In this chapter, we give a taste of the current state-of-the-art of LC-MS in clinical applications. Certainly not all possibilities and applications are discussed in this chapter. Topics discussed are therapeutic drag monitoring (Ch. 12.2) and neonatal screening (Ch. 13.2). In addition, the LC-MS analysis of various classes of drags of abuse, and systematic toxicological analysis are discussed. 

H.H. Maurer, Systematic toxicological analysis procedures for acidic drugs and/or metabolites relevant to clinical and forensic toxicology and/or doping control, J. Chromatogr. B, 733 (1999) 3. 

R. Jansen, G. Lachatre, P. Marquet, LC-MS-MS systematic toxicological analysis ... 

Maier RD, Bogusz M. Identification power of a standardized HPLC-DAD system for systematic toxicological analysis. J Ana Toxicol 1995 19 79-83. 

Fully-automated systematic toxicologic analysis of drugs, poisons, and metabolites in whole blood, urine and plasma by gas chromatography-fuh scan mass spectrometry. J Chromatogr 1998 713 265-79. 

Muller, C. Schafer, R Stortzel,M. Vogt, S. Weinmann, W. Ion Suppression Effects in Liquid Chromatography-Electrospray-Ionisation Transport-Region Collision Induced Dissociation Mass Spectrometry with Different Serum Extraction Methods for Systematic Toxicological Analysis with Mass Spectra Libraries, J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 773(1), 47-52 (2002). 

A set of 25 barbiturates was analyzed using CZE and MEKC. Buffers consisting of 90 mM borate, pH 8.4 (CZE), and 20 mM phosphate, 50 mM sodium dodecylsulfate (SDS), pH 7.5 (MEKC). The methods were evaluated for their suitability in systematic toxicological analysis (STA), especially when a combination of methods having a low correlation is used (305). A solid-phase microextraction device in combination with CE for the determination of barbiturates was described (see 306 and Sec. VII). The detection limit for 10 barbiturates was 0.1 ppm in urine, while the limit of detection was about 3 times poorer in bovine serum (306). Polyacrylamide-coated columns have been used for barbiturates and benzodiazepines. Seven kinds of barbiturates were sucessfully separated with the coated columns without further additives (307). The benzodiazepines, which are electrically neutral solutes, were separated in the presence of SDS. The CE method offered fast and efficient separations of the more hydrophobic solutes. 

CM Boone, JP Franke, RA de Zeeuw, K Ensing. Evaluation of capillary electrophoretic techniques towards systematic toxicological analysis. J Chromatogr A 838 259-272, 1999. 

Bogusz, M. Erkens, M. Maier, R.D. Schroder, I. Applicability of reversed-phase base-deactivated columns for systematic toxicological analysis. J.Liq.Chromatogr., 1992,15,127-150 [simultaneousbral-lobarbital, diphenhydramine, fluphenazine, imipramine, pentobarbital, salicylamide, secobarbital, thiopental, thioridazine]... 

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