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Toxicology: Methods of Analysis, Postmortem

OH Drummer, Victorian Institute of Forensic Medicine, Southbank, VIC, Australia and Monash University, Southbank, VIC, Australia
r 2016 Elsevier Ltd. All rights reserved.

Abstract

The analytical processes used to assess the presence of foreign substances in postmortem specimens require
consideration of a number of factors. The main specimen is blood, provided it is taken from a peripheral
site, such as the leg to reduce artefactual changes in concentration. Urine and vitreous humor should be
collected if available. Gastric contents and a section of liver should be also collected in some cases,
particularly suspected poisonings. Methods used for initial testing and confirmation are very similar to
antemortem drug investigations.

Glossary Procurator fiscal A legal officer in Scotland whose


Bioconversion The use of biological processes to function is to investigate cases of sudden death,
change the nature of a substance, for example, by amongst other duties.
enzymes in the liver or from enzymes in microbes. Redistribution A process occurring after death in
Intrathecal Injection into the spinal canal. which substances diffuse from one anatomical site to
Metabolism Process by which substances are another.
converted by the body into substances (metabolites)
that are often more easily excreted from the body than
the parent compound.

Introduction may involve corroboration of witness accounts of drug-


using behavior.
In postmortem cases, as with other forensic cases, tox- Typical drugs used are alcohol, amphetamines, co-
icology testing assists the investigating authorities in the caine, or one of the benzodiazepines (e.g., alprazolam,
investigation of a case. Ultimately, toxicology testing diazepam, flunitrazepam, etc.), or one of the other sed-
results assist the coroner, medical examiner, or the ating agents (e.g., zolpidem, sedating antidepressants,
procurator fiscal, whereas in other jurisdictions based on and antipsychotics). Victims or perpetrators of violent
common law various combinations of coroner and/or crime may also have consumed medication to treat
medical examiner systems apply, or an equivalent ju- a psychiatric problem or a host of other medical con-
dicial officer in other legal systems in establishing the ditions. The presence of drugs may therefore allude
evidence of any drug use. In cases where toxicology to such treatment, or at least confirm that the person
testing fails to detect foreign substances, it allows the concerned has taken their medication as prescribed. In
investigators to turn their attention to other relevant some cases, these medications may even have contrib-
factors, since a pathological examination usually does uted to behavioral problems (Drummer, 1998).
not show unambiguous indicia suggestive of drug use. In practice, it has been observed that deceased per-
Drug use can only be confirmed by the conduct of sons have often consumed two or more drugs, and in
appropriate analytical toxicology testing procedures on many cases the investigating authority (medical exam-
appropriate specimens. iner, police, coroner, etc.) is not aware of any or all the
Toxicology testing is particularly important in vic- drugs used. Since the majority of cases (470%) involve
tims of homicide in which drugs may have been given by more than one drug, it is advisable to conduct a
the assailant to reduce consciousness of the victim and in broad drug screening to include most of the common
cases in which drugs are likely to have been used by the drugs, rather than target the analysis to one or a limited
victim. In the latter scenario, modification of behavior range of drugs suggested by the circumstances. This also
and/or the state of mind by drug use may be important allows experts to determine whether any likely toxic
in criminal trials, not necessarily to mitigate the intent of effect is possible from the combined actions of the drugs
the accused, but primarily to reconstruct, as far as pos- or an adverse drug interaction may have occurred
sible, the events that led to the act. Such reconstruction (Levine, 1999; Moffat et al., 2004).

608 Encyclopedia of Forensic and Legal Medicine, Volume 4 doi:10.1016/B978-0-12-800034-2.00380-3


Toxicology: Methods of Analysis, Postmortem 609

Specimens may be significantly higher. Similarly, the blood should


be collected before the body is eviscerated, to avoid
The preferred specimens collected at postmortem will contamination.
depend on the type of case. Typically one or more blood Blood can also be taken by direct puncture of the
specimens and urine are collected, although as Table 1 relevant anatomical region and when this is allowed it is
illustrates, a number of other specimens should be preferable to take this specimen as soon as practicable,
taken in certain case types. A useful forensic technical well before the autopsy to minimize any postmortem
procedure in the autopsy suite is to take a ‘full’ set of changes (see later). When blood is obtained by direct
specimens, in all but the most obvious natural-cause puncture, the site of collection should be specified on the
investigations. This will avoid the embarrassment of specimen tube. Autopsy procedures should therefore
insufficient or inappropriate specimens collected in a accommodate the need to obtain optimal blood speci-
case and give the toxicologist the best chance to satis- mens for toxicological purposes.
factorily complete the analytical investigation. Against Blood stored at 4 1C can be used for a few days and is
this is the balance of the legal and cultural sensitivities preferred for alcohol and volatile substance analyses,
surrounding the collection and retention of tissue spe- however ideally blood collected for other purposes
cimens (Flanagan et al., 2005). should be stored frozen until analysis occurs (–20 1C or
lower), particularly for long-term storage after the cases
Blood analyses have been completed. This reduces decom-
positional changes of the specimen and reduces deg-
Blood is the most useful specimen that can be collected radation of drugs and poisons present in the specimen.
since drugs present in this fluid can best be related to a
physiological or pharmacological effect and can be used
to assess the likelihood of recent drug use or exposure to Urine
chemicals. A number of problems are associated with Urine is the second most important specimen collected.
the collection of this fluid in cadavers. Two 10-ml Since concentrations of drugs and metabolites of drugs
samples of blood are recommended, one to be used for are usually much higher than in blood, urine provides a
blood alcohol analyses and the other for blood toxicol- valuable specimen to screen for drug use over the pre-
ogy. The splitting of the two blood specimens reduces vious day or two. Urine can be collected after opening of
the possibility of contamination in the laboratory and the abdomen, or by direct puncture of the bladder. An
enables the blood alcohol specimen to be retained sep- autopsy is not necessary to collect this specimen.
arately to the other blood specimen(s). Forensic techni- Preservative can be added to urine, as for blood, al-
cians or pathologists should be aware that the collection though it is common not to add preservative. This spe-
of peripheral blood reduces the possibility of post- cimen should be analyzed within a few days when stored
mortem artifacts frustrating interpretation of any posi- at 4 1C, although it is preferable to store the specimen
tive results. The preferred collection site is the femoral frozen at –20 1C until use, particularly if the urine is not
vein (leg). However, failure to collect the specimen distal analyzed soon after receipt.
to a ligature or clamp applied to the femoral vein may
allow blood to be drawn down from the inferior vena
cava in the abdomen, where the concentration of drugs Vitreous Humor
Vitreous humor is an ideal fluid to accompany positive
Table 1 Recommended specimens for postmortem toxicology blood-alcohol cases, since the alcohol content of vitreous
testing is usually slightly higher than blood (about 20%) and
can prove useful to exclude putrefactive formation of
Case type Specimen
alcohol in blood, and visceral contamination. Vitreous
All cases Peripheral blood (10 ml) with humor is also a useful fluid for a range of drugs in-
fluoride 1% w/v cluding digoxin and antidepressants, as well as a number
Serum, no preservative of biochemical markers. Since vitreous humor can easily
Urine (up to 10 ml) be collected, it is strongly recommended that this speci-
Vitreous humor (2–5 ml)
men be included in a routine sudden death investigation.
Suspicious deaths As for all cases, plus portion of liver
(100 g), hair In pediatric cases, where the eyes may need to be
Suspected drug-related cases As for suspicious cases examined histologically for evidence of shaking, vitreous
Suspected volatile abuse As for suspicious cases plus tied- humor should only be taken after careful consideration.
off lung or lung fluid
Biochemical abnormalitiesa Serum (5 ml) plus vitreous humor
Heavy metal poisoning As for suspicious cases plus kidney Liver
a
This may include checks for dehydration (urea in vitreous), insulin in serum, The liver is traditionally a favored tissue for toxicologists
tryptase in serum, etc. since drugs are often found in higher concentrations than
610 Toxicology: Methods of Analysis, Postmortem

blood and the liver can be readily homogenized. All cases Other Specimens
of suspected drug use should have a portion of liver
Occasionally other specimens can provide valuable in-
collected. A 100 g aliquot is sufficient for most analyses.
formation in a case. Hair can provide a history of drug
The right lobe is preferred, since it is least subject to
use, or exposure to chemicals if chronic exposure is
postmortem diffusion of drug from the bowel contents
thought to have occurred. Hair can, therefore, provide
and the mesenteric circulation.
evidence of drug use for much longer periods of time
than urine. The relation between dose and hair con-
centration is poor, although some comparisons can be
Gastric Contents
made as to the extent of drug use, for example, regu-
Gastric contents are invaluable in cases of suspected larity of prescribed drugs or regularity of the use of
poisoning. The aim of using this specimen is to establish heroin.
the actual content of drug (or poison) remaining in this Bile can sometimes be a useful fluid for detecting
organ at death and gastric analysis may allow the route morphine or heroin use since biliary concentrations can
of drug administration to be determined. Drug residues be much higher than those in blood. A number of other
can be isolated out by direct extraction with methanol, drugs are found in bile in relatively high (and therefore
or another solvent, and analyzed by conventional more easily detectable) concentrations including colchi-
chromatographic techniques. When little or no fluid is cine, other opioids, benzodiazepines, and glucuronide
present in the stomach provision for the whole stomach metabolites. Bile may also occasionally be useful in late-
allows the analyst to dissolve any drug adhered to the stage paracetamol poisonings.
sides of the walls. Toxicologists should be aware that Samples of brain tissue may be more relevant for
small quantities of drug will derive from the bile, espe- some centrally active drugs such as morphine and other
cially during agonal processes, hence drug content in opioids, and skin (with associated subcutaneous tissue)
the stomach must not necessarily imply oral ingestion. may show large deposits of drugs left behind after an
Results should be reported in milligrams or grams in injection. When taking skin for the purpose of deter-
the total gastric content. If only an aliquot of gastric mining a likely injection site it is important that a control
contents is supplied the results may need to be reported site is also collected, for example, from the other arm.
as a concentration. However, gastric contents are rarely Results are normally expressed as milligrams per gram
homogeneous particularly after meals hence whole wet weight tissue.
contents are preferred wherever possible. Occasionally, Other specimens may be useful in specific circum-
pathologists will need to examine the stomach. This stances, for example, cerebrospinal fluid in medical
should be done prior to collection of any contents. matters involving intrathecally administered drugs.

Lungs Specimens from a Putrefied Body

Lung fluid (or tied-off lungs) is (are) recommended In cases of extreme putrefaction, the recommended list
in cases of suspected volatile substance abuse. Since of specimens will no longer be appropriate. Muscular
quantitative results are rarely interpretable, only ‘de- tissue, hair, and bone can be useful specimens in this
tected’ or ‘not detected’ results are usually sufficient type of case, although the physical state of the body will
(Table 2). In jurisdictions where tissue cannot be col- determine what specimens are available for collection.
lected or retained freely, blood from the pulmonary vein Body fluids will be present in some putrefied bodies,
or the left side of the heart can be used in this context. however this is no longer blood, but rather liquefied
tissues; however, this fluid can be used to screen for the
presence of drugs. Quantitative results are of little use in
Table 2 Applications specific to particular specimens badly putrefied cases (Drummer, 2010).
Specimen Useful target substances

Blood/urine/liver/gastric All drugs and poisons General Techniques


contents/hair
Bile Benzodiazepines, colchicine, morphine,
and other opioids A range of techniques is available to detect drugs in the
Brain Antipsychotics, opioids collected specimens (Maurer, 1992; Polettini, 1999).
Lungs (fluid contents) Volatile substances (hydrocarbons, For all drugs and poisons the specimens collected
solvents, etc.) postmortem are essentially identical to those collected
Serum Insulin and tryptasea antemortem. These range from commercial kit-based im-
Vitreous humor Alcohol, digoxin, creatinine, glucose, and munoassays (enzyme linked immunosorbent assay
urea
(ELISA), enzyme multiplied immunoassay technique
a
Marker for anaphylaxis. (EMIT), fluorescence polarization immunoassay (FPIA),
Toxicology: Methods of Analysis, Postmortem 611

cloned enzyme drug immunoassay (CEDIA), radio- most importantly, essentially eliminating matrix effects
immunoassay (RIA), etc.) to instrumental separation caused by poor recoveries of drug. While recoveries of
techniques such as high-performance liquid chroma- drug may vary from one matrix to another, and even
tography (HPLC) and gas chromatography (GC). Mass from calibrators, the deuterated internal standard will
spectrometry (MS) is the definitive technique to establish correct for this. For this reason, assays involving MS
proof of structure of an unknown substance and can be should use deuterated internal standards wherever pos-
linked to GC or HPLC. Even MS has its limitations, for sible in postmortem analyses.
example, special techniques may be needed to characterize The analyst should always be on the alert for unusual
phenethylamines that do not have sufficiently unique findings. For example, if a large acetone peak is seen in
spectra. an alcohol analysis this might suggest undiagnosed
The specimens analyzed in postmortem cases are most diabetes in life, or a peak not recognized as a drug in a
often blood and liver, rather than urine and serum that are library search on the MS may be evidence of an unusual
used in antemortem analysis and the other specimens listed or uncommon substance.
earlier. The use of blood and liver, and indeed all other
postmortem specimens, requires separate validation
against those methods used in antemortem analysis. The Recommended Techniques for Postmortem Analysis
methods used require modification to ensure a reliable
extraction recovery, a low level of interference, and re- As indicated before it is important that a drug screen
producible quantitative results. Special attention to these encompasses the widest number of drugs and poisons
factors is required on partly or fully putrefied specimens to without seriously compromising the ability of the la-
ensure no interference from endogenous substances. Cutoff boratory to provide a suitable turn-around time for the
values often used in workplace, sports, and drugs-of-abuse investigators. Urinalysis (or analysis on another speci-
testing in urine and oral fluid are no longer appropriate in men) using one of the commercial immunoassay is rec-
postmortem cases involving alternative specimens to urine. ommended for the main classes of drugs. These usually
Even postmortem urine should not normally be tested to include amphetamines, benzodiazepines, cannabinoids
cut-off limits used in drugs-of-abuse testing in living cases (cannabis metabolites), cocaine metabolite, and mor-
since the presence of a small concentration of drug may be phine like opioids (opiates). Other kits are available
of forensic significance. for 6-acetylmorphine (heroin metabolite), barbiturates,
The range of immunoassays used in antemortem buprenorphine, fentanyl, lysergic acid diethylamide,
analysis can also be used in postmortem analysis pro- methadone, oxycodone, and some of the emerging
vided suitable modification in the preparation of the drugs such as synthetic cannabinoids and cathinone
specimen occurs. Urine-based kits can be used for uri- stimulants.
nalysis, but blood or tissue homogenates require special In addition, a series of other (usually chromato-
treatment to remove matrix effects. Urine may be un- graphic) tests are strongly recommended. The schema
available in postmortem cases. ELISA techniques are the shown in Figure 1 illustrates a typical analytical profile
screening technique of choice for the direct analysis of for routine case screening on blood.
blood (and other specimens such as hair digests) for Blood is analyzed for alcohol and is subject to
drugs of abuse. False-positive results with immunoassays screening techniques aimed at capturing a wide selection
occur, either from structurally related drugs or from of ‘common’ chemical substances (drugs and poisons).
metabolites of other drugs that are recognized by the Only GC confirmation techniques are recommended for
antibodies or simply caused by the poor quality of the the analysis of alcohol (ethanol).
blood sample. While HPLC and GC techniques are more An acidic screen includes as many of the following
specific than immunoassays, any positive result must drugs in the various classes as possible: nonnarcotic
be confirmed by mass spectral identification, unless analgesics (e.g., paracetamol and aspirin), nonsteroidal
sufficient validation of another method has been con- anti-inflammatory drugs (naproxen, ketoprofen, ibu-
ducted to ensure courts of the reliability of the result. profen, etc.), diuretics (frusemide, hydrochlorothiazide,
Unconfirmed drug results, if reported, should be flagged etc.), anticonvulsants (carbamazepine, lamotrigine,
as presumptive, or by words of similar meaning. phenobarbital, phenytoin, valproate, etc.), antidiabetics
Solid-phase extraction (SPE) using small columns to (gliclazide, glibenclamide, metformin, etc.), barbiturates
selectively absorb drug from the matrix (e.g., Extrelut, (phenobarbital, pentobarbital, amylobarbital, etc.),
Sep-Pak, Bond-Elut, etc.) provides an excellent alter- benzodiazepines (alprazolam, diazepam, temazepam,
native to conventional liquid–liquid extraction techni- oxazepam, etc.), and the xanthines such as theophylline
ques. Solid-phase techniques have been published for and caffeine. The use of a solvent extraction technique
most analytes, tend to be quick, often provide clean at acidic pH or simple precipitation of blood proteins
extracts, and can be readily automated. The use of with 3-volumes of acetonitrile enables these substances
deuterated internal standards provides an ideal way to to be detected by gradient HPLC with photodiode array
monitor changes in chromatographic performance, and detection and/or by MS.
612 Toxicology: Methods of Analysis, Postmortem

Blood

Volatile analysis
Alcohol analysis Heavy metal analysis
Morphine analysis
Other specific analyses

1. Adjust to pH 2 and extract 1. Extract at pH 9−10 with butylchloride


2. Precipitate proteins 2. Solid-phase extraction pH 9−10
Acidic/neutral screen Basic/neutral screen

Apply to HPLC or GC Apply to GC-MS

Analgesics Amphetamines

Antiinflammatories Barbiturates

Antidiabetics Benzodiazepines

Benzodiazepines Antihistamines

Diuretics Antidepressants

Xanthines Cocaine

Herbicides Narcotics

Anticonvulsants Antipsychotics

Other acidic substances Organophosphates


Strychnine

Figure 1 Schematic showing extraction steps for blood analyses and substances classes likely to be detected. Reproduced from Drummer, O.H.,
2000. Toxicology: methods of analysis – Post mortem. In: Siegel, J.A., Saukko, P.J., Knupfer, G.C. (Eds.), Encyclopedia of Forensic Sciences.
London: Academic Press, pp. 1404–1409.

A basic extraction procedure using a solvent (e.g., array or multiwavelength) and MS provides excellent
butyl chloride but some others are also suitable), or detectability of a large range of chemical substances in-
an SPE procedure using octadecyl-bonded cartridges or cluding those not readily amenable to GC due to thermal
mixed-phase cartridges will provide a reasonably clean instability or high polarity.
extract from postmortem blood (and other tissues) for These two screening procedures will also enable a
analysis by capillary GC or HPLC. The use of an MS number of unusual poisons to be detected. For example,
detector is preferred (to allow simultaneous detection organophosphates and strychnine are readily detected
and confirmation), although a nitrogen phosphorous by GC separation techniques.
detector (NPD for nitrogen and phosphorous containing Poisons such as carbon monoxide (noxious gas
substances) compliments full-scan GC–MS. Electron in vehicle exhausts and fires) and hydrogen cyanide
capture detectors (ECD) on GC are extremely useful (noxious gas in fires) need special techniques. Carbon
for benzodiazepines. When using GC separation the use monoxide is measured by differential spectrophotometry
of dual detectors (NPD and MS, or NPD and ECD) of the carboxy hemoglobin complex in diluted blood
provides an additional degree of specificity and detection or by GC, while hydrogen cyanide (and cyanide salt
over one detector alone. When using HPLC separation exposure by converting to hydrogen cyanide) can be
the combined use of UV detection (usually photodiode measured by GC.
Toxicology: Methods of Analysis, Postmortem 613

Redistribution These processes are not limited to blood. Liver and


lung tissues show differences in the concentration with
In all postmortem analyses it is essential that any inter- time, again due to diffusion of drug from neighboring
pretation of results considers the process of redistri- sites and pooled blood.
bution. This affects all drugs in blood and tissues due to
disruption to the integrity of cellular membranes, caus-
ing alterations of drug concentrations within tissue Metabolism and Bioconversion
elements and diffusion from one tissue to another
(Pounder and Jones, 1990; Pounder, 1993). This process A number of drugs can undergo chemical changes in a
is particularly significant for drugs with high tissue body after death. These chemical changes can be either
concentrations including those drugs with high fat metabolically mediated or caused by spontaneous de-
solubility, since these drugs tend to show concentration gradative processes. For example, the metabolism of
differences in tissues and blood. Table 3 shows the ex- heroin to morphine occurs in life and in recently de-
tent of these changes for selected drugs when com- ceased persons by the action of blood and liver esterases.
parisons are made between blood collected from the For this reason, heroin is rarely detected in cadaveric
heart and that collected from the femoral region. The tissues. 6-Acetylmorphine is detected in urine for a few
femoral blood is least subject to redistribution after hours after last use. Morphine is the main target drug for
death; however, drugs with much higher concentrations most specimens. Aspirin is converted rapidly to salicyl-
in muscular tissue will still diffuse through the vessel ate by hydrolytic mechanisms. Most prodrugs activated
walls and elevate the neighboring blood concentration. by desterification or hydrolysis will be subject to similar
If the femoral vessels are not tied off from the vena cava processes.
and aorta then the process of drawing blood can also Nitro-containing drugs, such as the benzodiazepines,
extract blood from the abdominal cavity that has been nitrazepam clonazepam, flunitrazepam, and others
contaminated from diffusion of gastric and intestinal are also rapidly biotransformed after death to their
contents. It is therefore advisable to reduce these pro- respective amino metabolites by the action of certain
cesses by collecting blood specimens as soon as possible types of bacteria (obligate anaerobes) (Robertson and
after death from the femoral region with blood vessels Drummer, 1995). Toxicologists must therefore target
tied off to reduce contamination. In cases where death their analyses to these transformation products rather
has occurred in hospital it is recommended to obtain than the parent drug. Sulfur-containing drugs such as
specimens taken for clinical purposes immediately be- dothiepin, thiopental, thioridazine, etc., are also subject
fore death, or on admission to hospital, whichever is to bacterial attack during the postmortem interval
more appropriate. leading to progressive losses due to putrefaction. Of
course, the parallel process of tissue loss will also affect
Table 3 Likely extent of postmortem redistribution for selected the tissue concentration during putrefaction.
drugs and drug classes Chemical degradation occurs for a number of drugs
and metabolites even when specimens are stored frozen
Drug/drug class Likely extent of redistributiona
at –20 1C. For example, some benzodiazepines and
Acetaminophen (paracetamol) Low benzodiazepine metabolites and antipsychotics, such as
Alcohol (ethanol) Low thioridazine. For many drugs, complete stability char-
Antipsychotics Moderate acteristics have not yet been evaluated. Alcohol can also
Barbiturates Low be produced by bacterial action unless sealed tubes are
Benzodiazepines Low
stored frozen. The use of potassium fluoride as preser-
Cocaine Low
Digoxin High
vative (minimum 1% w/v) is required to prevent bac-
Fentanyl High terial activity for up to 1 month after collection, when
Ketamine Moderate stored at 4 1C.
3,4-Methylenedioxymethamphetamine Moderate
Methadone Moderate
Methamphetamine/amphetamine Moderate Reports
Morphine Low
Propoxyphene High
Serotonin reuptake inhibitors Moderate Once an analysis is complete, a report must be issued to
D9-Tetrahydrocannabinol Moderate the client(s) that accurately details the analytical find-
Tricyclic antidepressants High ings. These results should indicate the type of tests
a
conducted, the analytical method used (i.e., HPLC, GC–
Low, up to 25% elevation; moderate, up to 50% elevation; high, greater than 50%
elevation likely.
MS, etc.), on which specimens the analyses were con-
Note: These are only indicative measures and will depend greatly on time form death to ducted, and of course the result(s). The result(s) should
sampling, condition of body and sampling site (if femoral blood is not used extent of be unambiguous using such terms as ‘detected’ or ‘not
redistribution is likely to be higher). detected.’ The use of the term ‘not present’ should be
614 Toxicology: Methods of Analysis, Postmortem

avoided, since it implies no possibility of the substance References


being present. A toxicologist can rarely be so definitive
and can only indicate that a substance was not detected Drummer, O.H., 1998. Adverse drug reactions. In: Selby, H. (Ed.), The Inquest
at a certain threshold concentration. For this reason, a Handbook. Leichardt, NSW: Federation Press.
Drummer, O.H., 2010. Forensic toxicology. In: Luch, A. (Ed.), Molecular, Clinical
detection limit alongside tests for specific substances and Environmental Toxicology. Basel, Switzerland: Birkhauser Verlag,
should be provided for ‘not detected’ results. pp. 579–603.
For quantitative results, consistency in units is ad- Flanagan, R.F., Connally, J.G.C., Evans, J.M., 2005. Analytical toxicology: Guidelines
for sample collection postmortem. Toxicological Reviews 24 (1), 63–71.
vised and should not be given with more significant
Levine, B., 1999. Principles of Forensic Toxicology. Washington, DC: American
digits than the accuracy will allow. For example, there is Association of Clinical Chemistry.
no point in reporting a result for blood morphine as Maurer, H.H., 1992. Systematic toxicological analysis of drugs and their metabolites
0.162 mg l 1 when the accuracy and precision of the by gas chromatography-mass spectrometry. Journal of Chromatography 580,
3–41.
method is 720%. A result of 0.16 mg l 1 would suffice. Moffat, A.C., Osselton, D., Widdop, B., 2004. Clarke's Isolation and Identification of
For drug screening results it is advisable to provide cli- Drugs. London: The Pharmaceutical Press.
ents with an indication of the range of substances a Polettini, A., 1999. Systematic toxicological analysis of drugs and poisons in
method is capable of detecting, and some indication of biosamples by hyphenated chromatographic and spectroscopic techniques.
Journal of Chromatography B Biomedical Sciences and Applications 733, 47–63.
the detection limit, that is, ‘at least therapeutic concen- Pounder, D.J., 1993. The nightmare of postmortem drug changes. Legal Medicine
trations’ or ‘only supratherapeutic concentrations.’ 1993, 163–191.
To enable proper interpretation of evidence all re- Pounder, D.J., Jones, G.R., 1990. Post-mortem drug redistribution − a toxicological
nightmare. Forensic Science International 45, 253–263.
ports should indicate the site of blood sampling, and Robertson, M.D., Drummer, O.H., 1995. Postmortem drug metabolism by bacteria.
provide where relevant, some comment on the possi- Journal of Forensic Sciences 40, 382–386.
bility of postmortem artifacts such as redistribution.
By incorporating these comments, uninformed persons
reading the report are less likely to unwittingly mis- Relevant Websites
interpret the results.
www.soft-tox.org
Society of Forensic Toxicologists.
See also: Toxicology: Methods of Analysis, Antemortem www.tiaft.org
The International Association of Forensic Toxicologists.

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