SGMS Meeting 2000

GC-MS and LC-MS in clinical and forensic toxicology

Hans H. Maurer
Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, University of Saarland, D-66421 Homburg/Saar (Germany).

Specific and sensitive detection or precise quantification of xenobiotics in biosamples (e.g. blood, urine, saliva, sweat, hair) are great challenges in clinical and forensic toxicology. GC-MS is the most sensitive, specific and universal analytical method for low mass xenobiotics. Precise quantification can be performed using the selected ion mode (SIM) and stable isotopes as internal standards (1). Negative chemical ionization (NCI) can improve severalfold the sensitivity for the determination of compounds with electronegative sites (e.g. halogenes). For screening and identification of most of the basic and neutral drugs (e.g. drugs of abuse, psychotropics, hypnotics, analgesics, cardiacs) in urine, a systematic toxicological analysis procedure (STA) was developed using GC-MS after acid hydrolysis, extraction and acetylation (2-4). For detection of acidic drugs, poisons and metabolites in urine, a further GC-MS procedure was developed using extractive alkylation (4-6).

LC-MS with electrospray ionization techniques have become useful tools also in toxicology (7). APCI allows very sensitive determination of analytes with moderate polarity and molecular mass, like low-dosed benzodiazepines or opioids, new psychotropics. API-LC-MS allows the determination of high-polar and/or high-molecular analytes like toxic peptides (e.g. of amanita phalloides mushrooms in urine after immunoaffinity extraction (8)), nucleotides, high-molecular bacterial toxins or phase II metabolites. These examples show that in clinical and forensic toxicology GC-MS is the method of choice for low mass xenobiotics while LC-MS is that for non-volatiles.

(1) Maurer HH, Bickeboeller-Friedrich J, Kraemer T, Peters FT. Toxicokinetics and analytical toxicology of amphetamine-derived designer drugs ("Ecstasy"). Toxicol Lett 2000;112-113:133-142.

(2) Maurer HH, Bickeboeller-Friedrich J. Screening procedure for detection of antidepressants of the selective serotonin reuptake inhibitor (SSRI) type and their metabolites in urine as part of a modified systematic toxicological analysis (STA) procedure using gas chromatography-mass spectrometry (GC-MS). J Anal Toxicol 2000;24 (5), in press.

(3) Maurer HH. Procedures for simultaneous detection of several drugs used in the high throughput toxicological screening and doping control [review]. Comb Chem High Throughput Screen 2000, in press.

(4) Pfleger K, Maurer HH, Weber A, eds. Mass Spectral Lipary of Drugs, Poisons, Pesticides, Pollutants and their Metabolites. 3rd. ed. Palo Alto (CA): Agilent Technologies, 2000.

(5) Maurer HH, Arlt JW. Screening procedure for detection of dihydropyridine calcium channel blocker metabolites in urine as part of a systematic toxicological analysis procedure for acidics by gas chromatography-mass spectrometry (GC-MS) after extractive methylation. J Anal Toxicol 1999;23:73-80.

(6) Maurer HH. Systematic toxicological analysis procedures for acidic drugs and/or metabolites relevant to clinical and forensic toxicology or doping control [review]. J Chromatogr B 1999;733:3-25.

(7) Maurer HH. Liquid chromatography-mass spectrometry in forensic and clinical toxicology [review]. J Chromatogr B 1998;713:3-25.

(8) Maurer HH, Schmitt CJ, Weber AA, Kraemer T. Validated electrospray LC-MS assay for determination of the mushroom toxins alpha- and beta-amanitin in urine after immunoaffinity extraction. J Chromatogr B 2000, in press.