Page 15 - Advances in Forensic Applications of Mass Spectrometry - Jehuda Yinon

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1.1 Introduction

In forensic toxicology, proof of abuse of illegal drugs or of murder by poi-
soning are important tasks. Furthermore, drugs, which may reduce the penal
responsibility of a defendant, or which may reduce the fitness to drive a car,
must be monitored in body fluids or tissues.
In clinical toxicology, the diagnosis or the definite exclusion of an acute
or chronic poisoning is of great importance. Furthermore, patients addicted
to alcohol, medicaments, or illegal drugs have to be monitored. For deter-
mination of clinical death as a prerequisite for explantation of organs, the
presence of drugs which may depress the central nervous system must be
analytically excluded. The compliance of patients can be monitored by deter-
mination of the prescribed drugs. Finally, monitoring of drugs with a narrow
therapeutic range can be performed by the clinical toxicologist. Similiar
problems arise in forensic toxicology.
In doping control, the use or abuse of drugs that may stimulate the build-
up of muscles, enhance endurance during competition, lead to reduction of
body weight, or that may reduce pain caused by overexertion must be mon-
itored, typically in urine.
An efficient toxicological analysis is the basis of competent toxicological
judgement, consultation, and expertise. The choice of methods in analytical
toxicology depends on the problems to be solved. Usually, the compounds
to be analyzed are unknown. Therefore, the first step is the identification of
the compounds of interest which can then be quantified, e.g., in plasma. The
screening strategy of systematic toxicological analyses (STA) must be very
extensive because several thousands of drugs or pesticides have to be consid-
ered. It often includes screening and confirmatory tests. If only a single drug
or category has to be monitored, immunoassays can be used for screening
in order to differentiate between negative and presumptively positive samples.
Positive results must be confirmed by a second independent method that is
at least as sensitive as the screening test and that provides the highest level
of confidence in the result. Without doubt, GC/MS, especially in the full-
scan electron ionization (EI) mode, is still the reference method for confir-
mation of positive screening tests. 1–21 Nevertheless, LC/MS has also been
applied for screening and confirmation of particular drugs or drug classes,
especially in blood. 22–31
The two-step strategy, immunoassay screening and MS confirmation, is
employed only if those drugs or poisons have to be determined that are
scheduled, e.g., by law or by international organizations, and for which
immunoassays are commercially available. If this is not the case, the screening
strategy must be more extensive, because several thousands of drugs or
pesticides are on the market worldwide. For these reasons, STA procedures
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