Clinical-toxicological analysis

R.A. de Zeeuw, J.P. Franke, F. Degel, G. Machbert, H. Schutz, J. Wijsbeek (Eds.), Thin layer chromatographic Rf values of Toxicologically Relevant Substances on Standardized Systems, 2nd ed., VCH, Weinheim, 1992, Report XVII of the DFG Commission for Clinical-Toxicological Analysis. 

Forschungsgemeinschaft, Weinheim, 2002 Report XVIII of the DFG Commission for Clinical-Toxicological Analysis. 

Routine analysis of common designer drugs in human biological fluids (e.g., plasma, urine) is a major concern in doping control, surveillance of drug substitution, clinical toxicology, as well as forensic science.Method sensitivity is often an issue since many drugs... 

Most of the published analytical methods for the determination of antidepressants were developed in plasma, serum, whole blood, and urine, which are the most useful matrices for clinical and toxicological analysis of these therapeutic compounds. However, albeit few, some LC-MS methodologies have also been described for the analysis of several antidepressants in hair [30-33], oral fluid [34, 35], breast milk [36], or typical forensic matrices such as gastric content, bile, vitreous humor, brain, liver, lung, and/or muscle [37 10],... 

Plasma is the main biological sample used in clinical and toxicological analysis, as concentrations found in this matrix are correlated to the pharmacological effect, as well as to the side and toxic effects. However, oral fluid has also been employed in some specific applications because of the advantages associated to this alternative specimen easy, painless, and noninvasive collection, which does not require qualified personnel, it represents the free analyte fraction, and it has a window of detection similar to that in plasma. Within the possible applications of oral fluid analysis, two are of special relevance ... 

The toxicological analysis is essential in the clinical and medicolegal process, aimed at seeking evidence of the presence of psychoactive substances in biological fluids and tissues. The fields of intervention of a clinical toxicology laboratory are mainly two ... 

Clinical toxicology, where the analysis is made with a therapeutic purpose. 

A review of 139 methadone-related deaths between 1998 and 2002 in Palm Beach County supported those of previous investigations and suggested that it is not possible to establish a definitive lethal methadone blood concentration range. Methadone-related death is usually associated with the use of other drugs and toxicological analysis in such cases should be contextualized by the clinical circumstances surrounding the event and even a few months before the incident occurred (50). 

Baumgartner, W. A. and Hill, V. A., Hair analysis for drugs of abuse decontamination issues, in I. Sunshine, ed.. Recent Developments in Therapeutic Drug Monitoring and Clinical Toxicology, Marcel Dekker, New York, 1992, pp. 577-597. 

Technically, testing of hair for drugs is no more difficult or challenging than testing in many other "alternative" matrices (for example, liver, bone, etc.). In fact, the application of analytical methods and instrumental approaches are in most cases quite similar, regardless of the initial matrix. At present, hair analysis is routinely used as a tool for detection of drug use in forensic science, traffic medicine, occupational medicine, and clinical toxicology. 

Barnett, P., Rosenberry, T.L. (1977). Catalysis of acetylcholinesterase acceleration of the hydrolysis of neutral acetic acid esters by certain aromatic cations. J. Biol. Chem. 252 7200-6. Benz, R.D. (2007). Toxicological and clinical computational analysis and the US FDA/CDER. Expert Opin. Drug Metab. Toxicol. 3 109-24. 

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. 

Litovitz T, Clancy C, and Korberly B (1997) Surveillance of loperamide ingestions An analysis of 216 poison center reports. Clinical Toxicology 35(1) 11-19. 

Almost all of the above mentioned publications referred to bioanalytical methods for bioavailability, bioequivalence or pharmacokinetic studies. This field is of course very closely related to forensic and clinical toxicology, especially if only routine methods are considered. Therefore, it seems reasonable to base the discussion concerning method validation in toxicological analysis on the experiences and consensus described above and not to start the whole discussion anew. In the following, possible implications for forensic and clinical toxicology will be discussed. 

The same approaches and criteria as those described above under Limits could be used. All approaches have been described to a lesser or greater extent in international publications, especially for the determination of LOD. Nevertheless, it seems important to reach consensus on this matter at least for forensic and clinical toxicology, as reliable detection of a substance is one of the most important issues in toxicological analysis. At this point it must be stressed that for the estimation of LOD and LLOQ via a special calibration curve, the calibration samples must only contain the analyte at concentrations close to LOD and LLOQ. Use of the calibration curve over the whole range may lead to overestimation of these limits. 

Speed of analysis, or turnaround time (TOT), is a critical issue in clinical toxicology. A drug analysis that requires several hours to complete or that is not available at aU hours... 

Baumgartner WA, HiU VA. Hair analysis for drugs of abuse Decontamination issues. In Sunshine I ed. Recent developments in therapeutic drug monitoring and clinical toxicology. New York Marcel Dekker Inc, 1992 577-97. 

Brett AS. Implications of discordance between clinical impression and toxicology analysis in drug overdose. Arch Intern Med 1988 148 437-41. 

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