Fundamentals of Analytical Toxicology. Robin Whelpton

poisoned patients on the basis of suspicion and history rather than await the results of a laboratory test, but may change their approach once they have the result. The treatment of paracetamol poisoning is an example.

      Circumstantial evidence of the compound(s) involved in a poisoning episode is often ambiguous and thus, on the rare occasions when an analysis for ‘poisons’ is indicated, it is advisable to perform a ‘poisons screen’ routinely in all but the simplest cases. Similarly, the analysis should not end after the first positive finding because additional, hitherto unsuspected compounds may be present. An exception is sub-lethal carbon monoxide poisoning, which can be difficult to diagnose even if carboxyhaemoglobin measurements are available – circumstantial evidence of poisoning may prove invaluable in such cases. Of course, a positive result on a ‘poisons screen’ does not of itself confirm poisoning because such a result may arise from incidental or occupational exposure to the poison in question, or the use of drugs in treatment.

      Blood is often the easiest specimen to obtain from an unconscious patient and is needed for any quantitative measurements. Urine is also a valuable specimen not only because relatively large volumes are often available, but also because it is by far the easiest specimen to obtain, especially from patients likely to have damaged veins. Moreover, some compounds may be detected in urine after they have been cleared from blood. In addition, human urine presents less of a hazard than blood to laboratory staff. However, some compounds such as many benzodiazepines are extensively metabolized prior to excretion and then blood plasma is the specimen of choice for detecting the parent compound. Quantitative measurements in urine are generally of little use in emergency toxicology.

All poisons screens have limitations (Table 1.7). Thus, of the drugs commonly used to treat depression, lithium has to be looked for specifically, whilst those monoamine oxidase inhibitors (MAOIs) that act irreversibly, such as phenelzine, have a prolonged action in the body even though plasma concentrations are very low after overdosage. Any drug that is not bound to the enzyme may be excreted rapidly and may be difficult to detect except in a urine specimen obtained soon after the event. Tricyclic antidepressants are very lipophilic hence urinary concentrations, even after fatal poisoning, may be below the LLoD of the analytical method if death has occurred relatively soon after the ingestion. Poisoning with endogenous substances such as sodium and potassium is likewise often very difficult to diagnose (Belsey & Flanagan, 2016).

Table 1.7 Some analytes not normally included in analytical toxicology screens

Anabolic steroids	Heavy/toxic metal ions (antimony, arsenic, cadmium, lead, mercury)
Anticoagulants (apixaban, dabigatran, rivaroxaban, warfarin)	γ-Hydroxybutyrate (GHB)
Baclofen	Hypoglycaemic agents (gliclazide, insulin, metformin)
Carboxyhaemoglobin	Iron salts
Chloral hydrate	Laxatives (phenolphthalein)
Digoxin and other Digitalis glycosides	Lithium ion
2,4-Dinitrophenol (DNP)	Organophosphorus and other pesticides
Diuretics (furosemide, chlortalidone)	Thallium ion
Ethylene glycol (1,2-ethanediol)	Volatile compounds (butane, nitrous oxide)
Fungal/plant toxins (α-amanitin)

       1.4.2 Forensic toxicology

Toxicological investigations of deaths (including deaths in road traffic accidents) are often undertaken if there is a possibility that drugs or other poisons may have been involved. These include instances where deliberate poisoning, including self-poisoning, is a possibility, especially if death has occurred in children or whilst in police custody, or when decomposition has taken place to such an extent that it is difficult to glean much information as to the cause of death from a conventional post-mortem examination. The value of giving as full a clinical, occupational, or circumstantial history as possible, together with a copy of the post-mortem report, if available, when submitting samples for analysis cannot be overemphasized. Not only might this help target the analysis to likely poisons, but also the interpretation of any analytical results may be greatly simplified.

      Non-fatal incidents where toxicological investigations may be useful include collapse whilst in custody, alleged offences under road traffic legislation involving ethanol or other drugs, allegations of poisoning of relatives or pets, doping in sex offences, and other cases of assault. It may also be important to analyze samples from a suspect for the presence of drugs such as ethanol, which may have altered his or her perception or behaviour during the course of a crime.

      The specimens available may range from fresh blood to decomposing tissues recovered from a partial skeleton, while the quantity available may range from a kilogram of liver to a dried blood stain. Difficult areas still include screening for a wide range of compounds which could affect driving performance in, say, 2 mL of whole blood while leaving sufficient sample for a quantitative measurement, and detecting drugs used in sexual or other assaults (drug facilitated crime, DFC). Detailed guidelines as to sample collection and the scope of the analyses required in this latter case are available (UNODC, 2011).

An important role of the Coroner in England and Wales, of the Procurator Fiscal in Scotland, and of the Medical Examiner or equivalent in other jurisdictions is to establish how the deceased came by their death. The data derived from such investigations may be invaluable in monitoring the incidence of fatal poisoning. The importance of adequately documenting all acute poisoning incidents both in the hospital notes and in the laboratory records becomes clear when it is remembered that even an apparently trivial case may eventually be reviewed in detail in a coroner's or other court. Required documentation includes correctly recorded patient and sample details, the date and time of collection of samples, details of physical examination, nature and timing of treatment, particularly drug treatment, results of investigations (including units), and conversations with poisons information services and the laboratory. The laboratory should fully document all analyses and keep copies of all the reports issued. Residues of samples should be kept, appropriately stored, e.g. at –20 °C, until the conclusion of the investigation.

      In assessing the evidence of the analytical toxicologist, courts of law are concerned especially with the experience of the analyst, the origin and condition of the samples, and the analytical methods used. The ability to prove continuous and proper custody of the specimen is important. It used to be argued that evidence from a minimum of two unrelated analytical methods should be employed before a tentative identification is accepted, but with the advent of GC-MS and LC-MS methods this is often no longer the case, the MS data being regarded as orthogonal to the chromatographic data. The results should be presented together with sufficient information to ensure accurate interpretation of the findings by a coroner, magistrate, judge, and/or jury. There is always the possibility of an independent examination by a further expert instructed by another party in the case.

       1.4.3 Testing for substance misuse

      The value of blood, breath, or urinary measurements in the diagnosis of ethanol misuse and in monitoring abstinence is clear. Screening for substance misuse in urine is also valuable in monitoring illicit drug taking in dependent patients and guards against prescribing controlled drugs for patients who are not themselves drug dependent. Some substances disappear from biological samples very rapidly