The toxicologic investigation typically begins with the preliminary identification of drugs or chemicals present in postmortem specimens.30-39 Confirmatory testing is then performed to conclusively identify the substance(s) present in the postmortem specimens. In a forensic laboratory, positive identification must be established by at least two independent analyses, each based on a different analytic principle. The next step in the process is to determine the quantity of substance in the appropriate specimens. Identifying drugs in waste fluids, such as bile and urine, is a useful undertaking, but quantifying drugs in these fluids usually has limited interpretive value. Drug quantification in peripheral blood, along with quantification in samples from liver, gastric contents, or other specimens, as dictated by the case, provides more meaningful interpretive information.
Therapeutic and toxic ranges have been established for many compounds,28 but it should be recognized that "therapeutic" concentrations rarely can be determined in the postmortem setting.40
All cases cannot be tested for all drugs. A number of factors, some not immediately obvious, determine what kind, and how many, tests will be done. The importance of the medicolegal classification of death and specimen collection has already been mentioned. But other factors, such as geographic patterns of drug use and laboratory capabilities, must also be considered.
Occasionally, mere detection of a drug is sufficient. But, in the case of some prescription medications, the actual amount present must be quantified. A request for "therapeutic" drug analysis may be made even if the autopsy has already determined the cause of death. If a history of seizure is obtained, the pathologist may request an antiepileptic drug screen to determine whether or not the person was taking any such medication. The same holds true for, e.g., theophylline in individuals with asthma. An individual who has committed suicide may have been prescribed therapeutic drugs for depression or other mental illness. A test for these drugs may indicate the degree of patient compliance. In forensic toxicology, a negative laboratory result carries the same weight as a positive result.
Often the nature of a suspected toxin is unknown. This type of case is termed a "general unknown."41,42 In cases of this nature, a full analysis of all available specimens by as many techniques as possible may be required to reach a conclusion. The most common approach involves first testing for volatile agents, and then performing drug screens. The drug screen is usually confined to those drugs that are commonly seen in the casework. When the most common substances have been ruled out, the laboratory proceeds to test for more exotic drugs and poisons.
It is impossible to consider the topic of forensic toxicology without discussing analytical toxicology in detail.43-46 Screening methods should provide presumptive identification, or at least class identification while also giving an indication of concentration. An adequate screening protocol, capable of detecting or eliminating the majority of the commonly encountered toxins, usually requires a combination of three or more chemically unrelated techniques. In general, some toxins are so common that, no matter the type of case, they should always be included for analysis; e.g., ethanol, salicylate, acetaminophen, sedatives, hypnotics, and other drugs such as cocaine, opiates, and antidepressants. All screening tests that are positive for substances relevant to the case must then be confirmed, and analytes of significance submitted for quantification in several tissues. Later sections in this chapter discuss testing methods and how they are combined to yield effective analytical strategies.
During the toxicological investigation, each case is subjected to periodic review, its status evaluated, and the need for additional testing determined. Based on what is known about the death and the specimens available, a panel of screening tests is designed to quickly detect or rule out the most common drugs and, when appropriate, poisons.33,37,38,43,47 New tests may be ordered to expand the initial search, or to confirm preliminary findings.
The flow of information in forensic toxicology must be in two directions48 — from pathologist to laboratory, then back to the physician who will integrate all of the findings. Laboratory personnel must effectively communicate with the pathologist concerning the scope (and limitations) of the services they can provide, suggest the proper selection of specimens, and assist with interpretation of the results. In particular, when drug screens are used, the pathologist should know which drugs they cover — and which drugs will go undetected. To operate effectively, the toxicologist must be provided with enough information about the history and autopsy findings to rationally select the most appropriate tests.
Each laboratory must formulate and adhere to a quality assurance (QA) program. QA provides safeguards to ensure that the toxicology report contains results that are accurate and reproducible, and that the chain of custody has been preserved. A written QA plan sets out the procedures employed to ensure reliability, and provides the means to document that those procedures were correctly followed. The laboratory's strict adherence to a proper QA program induces confidence in the laboratory's work product and prevents or overcomes potential legal challenges. Before a new or improved method is introduced into a laboratory, it must be selected with care and its performance must be rigorously and impartially evaluated under laboratory conditions.
When all toxicological testing is completed, the results are summarized in a report that is sent to the pathologist. This report becomes a part of the autopsy report. It specifies the name of the deceased, if known, and the medical examiner case number. The specimens tested, the substances detected in each specimen, and the measured concentrations of those substances are presented in tabular form. The report should also list substances tested for, but not found, especially if they were named in the toxicology request. If any drug was detected, but not confirmed, a note to that effect should be on the report. In addition, any information about the specimens, such as the date and time of collection of ante-mortem blood or any unusual condition of a specimen, should also be noted on the report. Because of the well-known difficulties associated with the postmortem redistribution of many drugs, the report should always indicate where in the body the blood specimen was obtained. Toxicology reports are usually signed or initialed by the issuing toxicologist, and in some jurisdictions may be signed by the pathologist as well.
1.4.6 Toxicological Interpretation
All substances are poisons; there is none which is not a poison. The right dose differentiates a poison and a remedy.
Poisons and medicines are oftentimes the same substance given with different intents.
Peter Mere Latham (1789-1875)
The significance of the reported results must be explained, often to a jury.5,28,43,48-51 The pharmacology, toxicology, local patterns of drug abuse, and postmortem changes all can affect toxico-logical results. In any given case, a toxicologist may be asked the following questions (even though a definitive answer may not be possible in all instances):
2. Was the drug or combination of drugs sufficient to kill or to affect behavior?
3. What are its effects on behavior?
4. Does the evidence indicate if a substance was taken for therapeutic purposes, as a manifestation of drug misuse, for suicidal purposes, or was it administered homicidally?
5. Was the deceased intoxicated at the time of the incident that caused death?
6. How would intoxication by the particular drug manifest?
7. Is there any alternative explanation for the findings?
8. What additional tests might shed light on the questions?
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