Forensic toxicology
From The Art and Popular Culture Encyclopedia
| Revision as of 14:32, 3 May 2012 Jahsonic (Talk | contribs) ← Previous diff |
Current revision Jahsonic (Talk | contribs) |
||
| Line 1: | Line 1: | ||
| {{Template}} | {{Template}} | ||
| - | The '''Marsh test''' is a highly sensitive method in the detection of [[arsenic]], especially useful in the field of [[forensic toxicology]] when arsenic was used as a [[poison]]. It was developed by the chemist [[James Marsh (chemist)|James Marsh]] and first published in 1836. | + | '''Forensic toxicology''' is the use of [[toxicology]] and other disciplines such as [[analytical chemistry]], [[pharmacology]] and [[clinical chemistry]] to aid medical or legal investigation of death, poisoning, and drug use. The primary concern for forensic toxicology is not the legal outcome of the toxicological investigation or the technology utilised, but rather the obtaining and interpreting of the results. A toxicological analysis can be done to various kinds of samples. |
| - | Arsenic, in the form of white [[arsenic trioxide]] As<sub>2</sub>O<sub>3</sub>, was a highly favored poison, for it is odorless, easily incorporated into food and drink, and before the advent of the Marsh test, untraceable in the body. In France, it came to be known as ''poudre de succession'' ("inheritance powder"). For the untrained, [[arsenic poisoning]] would have symptoms similar to [[cholera]]. | + | A forensic toxicologist must consider the context of an investigation, in particular any physical symptoms recorded, and any evidence collected at a crime scene that may narrow the search, such as pill bottles, powders, trace residue, and any available chemicals. Provided with this information and samples with which to work, the forensic toxicologist must determine which toxic substances are present, in what concentrations, and the probable effect of those chemicals on the person. |
| - | == Precursor methods == | + | Determining the substance ingested is often complicated by the body's natural processes (see [[ADME]]), as it is rare for a chemical to remain in its original form once in the body. For example: [[heroin]] is almost immediately [[metabolism|metabolised]] into another substance and further to [[morphine]], making detailed investigation into factors such as injection marks and chemical purity necessary to confirm diagnosis. The substance may also have been diluted by its dispersal through the body; while a pill or other regulated dose of a drug may have [[grams]] or [[milligrams]] of the active constituent, an individual sample under investigation may only contain [[microgram]]s or [[nanogram]]s. |
| - | The first breakthrough in the detection of arsenic poisoning was in 1775 when [[Carl Wilhelm Scheele]] discovered a way to change arsenic trioxide to garlic-smelling [[arsine]] gas (AsH<sub>3</sub>), by treating it with [[nitric acid]] (HNO<sub>3</sub>) and combining it with [[zinc]]. | + | ==Samples== |
| + | ===Urine=== | ||
| + | A [[urine]] sample is urine that has come from the bladder and can be provided or taken post-mortem. | ||
| - | :As<sub>2</sub>O<sub>3</sub> + 6 Zn + 12 HNO<sub>3</sub> → 2 AsH<sub>3</sub> + 6 Zn(NO<sub>3</sub>)<sub>2</sub> + 3 H<sub>2</sub>O | + | ===Blood=== |
| + | A [[blood]] sample of approximately {{convert|10|ml|2|abbr=on}} is usually sufficient to screen and confirm most common toxic substances. A blood sample provides the toxicologist with a profile of the substance that the subject was influenced by at the time of collection; for this reason, it is the sample of choice for measuring [[blood alcohol content]] in [[drunk driving]] cases. | ||
| - | In 1787, [[Johann Daniel Metzger|Johann Metzger]] discovered that if arsenic trioxide was heated in the presence of [[charcoal]], a shiny black powder (arsenic mirror) would be formed over it. This is the reduction of As<sub>2</sub>O<sub>3</sub> by [[carbon]]: | + | ===Hair sample=== |
| + | [[Hair]] is capable of recording medium to long-term or high dosage substance abuse. Chemicals in the bloodstream may be transferred to the growing hair and stored in the [[hair follicle|follicle]], providing a rough [[Chronology|timeline]] of drug intake events. Head hair grows at rate of approximately 1 to 1.5 cm a month, and so cross sections from different sections of the follicle can give estimates as to when a substance was ingested. Testing for drugs in hair is not standard throughout the population. The darker and coarser the hair the more drug that will be found in the hair.If two people consumed the same amount of drugs, the person with the darker and coarser hair will have more drug in their hair than the lighter haired person when tested. This raises issues of possible racial bias in substance tests with hair samples. | ||
| - | : 2 As<sub>2</sub>O<sub>3</sub> + 3 C → 3 CO<sub>2</sub> + 4 As | + | ===Oral fluid=== |
| + | [[Oral fluid]] is the proper term, however [[saliva]] is used commonly. Saliva is a component of oral fluid. Oral fluid is composed of many things and concentrations of drugs typically parallel to those found in blood. Sometimes referred to as ultra filtrate of blood, it is thought that drugs pass into oral fluid predominantly through a process known as [[passive diffusion]]. Drugs and pharmaceuticals that are highly protein bound in blood will have a lower concentration in oral fluid. The use of oral fluid is gaining importance in forensic toxicology for showing recent drug use, e.g. in clinical settings or investigation of driving under influence of substances. | ||
| - | In 1806, [[Valentin Rose (pharmacologist)|Valentin Rose]] took the stomach of a victim suspected of being poisoned and treated it with [[potassium carbonate]] (K<sub>2</sub>CO<sub>3</sub>), [[calcium oxide]] (CaO) and nitric acid. Any arsenic present would appear as arsenic trioxide and then could be subjected to Metzger's test. | + | ===Other=== |
| + | Other bodily fluids and organs may provide samples, particularly samples collected during an [[autopsy]]. A common autopsy sample is the [[gastric content]]s of the deceased, which can be useful for detecting undigested pills or liquids that were ingested prior to death. In highly decomposed bodies, traditional samples may no longer be available. The [[vitreous humour]] from the eye may be used, as the fibrous layer of the eyeball and the eye socket of the skull protects the sample from trauma and adulteration. Other common organs used for toxicology are the brain, liver, and spleen. | ||
| - | However, the most common test (and used even today in water test kits) was discovered by [[Samuel Hahnemann]]. It would involve combining a sample fluid with [[hydrogen sulfide]] (H<sub>2</sub>S) in the presence of [[hydrochloric acid]] (HCl). A yellow precipitate, [[arsenic trisulfide]] (As<sub>2</sub>S<sub>3</sub>) would be formed if arsenic were present. | + | The inspection of the contents of the stomach must be part of every postmortem examination if possible because it may provide qualitative information concerning the nature of the last meal and the presence of abnormal constituents. Using it as a guide to the time of death, however, is theoretically unsound and presents many practical difficulties, although it may have limited applicability in some exceptional instances. Generally, using stomach contents as a guide to time of death involves an unacceptable degree of imprecision and is thus liable to mislead the investigator and the court. |
| + | Characteristic cell types from food plants can be used to identify a victim's last meal; knowledge about which can be useful in determining the victim's whereabouts or actions prior to death (Bock and Norris, 1997). Some of these cell types include (Dickison, 2000): | ||
| + | * sclereids (pears) | ||
| + | * starch grains (potatoes and other tubers) | ||
| + | * [[raphide]] crystals (pineapple) | ||
| + | * [[druse (botany)|druse]] crystals (citrus, beets, spinach) | ||
| + | * silica bodies (cereal grasses and bamboos) | ||
| + | In a case where a young woman had been stabbed to death, witnesses reported that she had eaten her last meal at a particular fast food restaurant. However, her stomach contents did not match the limited menu of the restaurant, leading investigators to conclude that she had eaten at some point after being seen in the restaurant. The investigation led to the apprehension of a man whom the victim knew, and with whom she had shared her actual final meal (Dickison, 2000). | ||
| + | Time since death can be approximated by the state of digestion of the stomach contents. It normally takes at least a couple of hours for food to pass from the stomach to the small intestine; a meal still largely in the stomach implies death shortly after eating, while an empty or nearly-empty stomach suggests a longer time period between eating and death (Batten, 1995). However, there are numerous mitigating factors to take into account: the extent to which the food had been chewed, the amount of fat and protein present, physical activity undertaken by the victim prior to death, mood of the victim, physiological variation from person to person. All these factors affect the rate at which food passes through the digestive tract. Pathologists are generally hesitant to base a precise time of death on the evidence of stomach contents alone. | ||
| - | == Circumstances and methodology == | + | ===Other organisms=== |
| + | [[Bacteria]], [[maggots]] and other organisms that may have ingested some of the subject matter may have also ingested any toxic substance within it. | ||
| - | Even so, these tests have proven not to be sensitive enough. In 1832, a certain John Bodle was brought to trial for poisoning his grandfather by putting arsenic in his coffee. [[James Marsh (chemist)|James Marsh]], a chemist working at the [[Royal Arsenal]] in [[Woolwich]] was called by the prosecution to try to detect its presence. He performed the standard test by passing hydrogen sulfide through the suspect fluid. While Marsh was able to detect arsenic, the yellow precipitate did not keep very well, and by the time it was presented to the jury it deteriorated. The jury was not convinced, and John Bodle was acquitted. | + | ==Detection and Classification== |
| - | Angered and frustrated by this, especially when John Bodle confessed later that he indeed killed his grandfather, Marsh decided to devise a better test to demonstrate the presence of arsenic. Taking Scheele's work as a basis, he constructed a simple glass apparatus capable of not only detecting minute traces of arsenic but also measuring its quantity. Adding a sample of tissue or body fluid to a glass vessel with zinc and acid would produce arsine gas if arsenic was present, in addition to the hydrogen that would be produced regardless by the zinc reacting with the acid. Igniting this gas mixture would oxidize any arsine present into arsenic and water vapor. This would cause a cold ceramic bowl held in the jet of the flame to be stained with a silvery-black deposit of arsenic, physically similar to the result of Metzger's reaction. The intensity of the stain could then be compared to films produced using known amounts of arsenic. Not only could minute amounts of arsenic be detected (as little as 0.02 mg), the test was very specific for arsenic. Although [[antimony]] (Sb) could give a false-positive test by forming a similar black deposit, it would not dissolve in a solution of [[sodium hypochlorite]] (NaOCl), while arsenic would. | + | Detection of drugs and pharmaceuticals in biological samples is usually done by an initial screening and then a confirmation of the compound(s), which may include a quantitation of the compound(s). The screening and confirmation are usually, but not necessarily, done with different analytical methods. Every analytical method used in forensic toxicology should be carefully tested by performing a validation of the method to ensure correct and indisputable results at all times. A testing laboratory involved in forensic toxicology should adhere to a quality programme to ensure the best possible results and safety of any individual. |
| - | == Specific reactions involved == | + | The choice of method for testing is highly dependent on what kind of substance one expects to find and the material on which the testing is performed. Biological samples are more complex to analyze because of factors such as the [[matrix effect]] and the metabolism and conjugation of the target compounds. |
| - | The Marsh test treats the sample with sulfuric acid and arsenic-free zinc. Even if there are minute amounts of arsenic present, the zinc reduces the [[trivalent]] arsenic (As<sup>3+</sup> ). Here are the two half-reactions: | + | ===Gas chromatography=== |
| + | [[Gas-liquid chromatography]] is of particular use in examining volatile [[organic compound]]s. | ||
| - | : Oxidation: Zn → Zn<sup>2+</sup> + 2 e<sup>−</sup> | + | ===Detection of Metals=== |
| - | : Reduction: As<sub>2</sub>O<sub>3</sub> + 12 e<sup>−</sup> + 6 H<sup>+</sup> → 2 As<sup>3−</sup> + 3 H<sub>2</sub>O | + | The compounds suspected of containing a [[metal]] are traditionally analyzed by the destruction of the organic matrix by chemical or thermal oxidation. This leaves the metal to be identified and quantified in the inorganic residue, and it can be detected using such methods as the [[Reinsch test]], emission [[spectroscopy]] or [[X-ray diffraction]]. Unfortunately, while this identifies the metals present it removes the original compound, and so hinders efforts to determine what may have been ingested. The [[Toxicity|toxic effects]] of various metallic compounds can vary considerably. |
| - | Overall, we have this reaction: | + | ===Nonvolatile organic substances=== |
| + | Drugs, both prescribed and illicit, [[pesticide]]s, natural products, [[pollutant]]s and industrial compounds are some of the most common nonvolatile compounds encountered. Screening methods include [[thin-layer chromatography]], [[gas-liquid chromatography]] and immunoassay. For complete legal identification, a second confirmatory test is usually also required. The trend today is to use liquid chromatography tandem mass spectrometry, predeced with sample workup as liquid-liquid extraction or solid phase extraction. Older methods include: [[spot test]] (see [[Pill testing]]), typically the [[Marquis reagent|Marquis Reagent]], [[Mecke Reagent]], and [[Froehde's reagent]] for [[opiates]], [[Marquis reagent|Marquis Reagent]] and [[Simon's reagent]] for [[amphetamine]], [[methamphetamine]] and other analogs, like [[MDMA]], the [[Scott's test]] for cocaine, and the modified [[Duquenois-Levine reagent|Duquenois]] reagent for [[cannabis (drug)|marijuana]] and other [[cannabinoids]]. For compounds that don't have a common spot test, like [[benzodiazepines]], another test may be used, typically [[mass spectrometry]], or [[spectrophotometry]]. | ||
| - | : As<sub>2</sub>O<sub>3</sub> + 6 Zn + 6 H<sup>+</sup> → 2 As<sup>3−</sup> + 6 Zn<sup>2+</sup> + 3 H<sub>2</sub>O | + | ==See also== |
| - | + | *[[Arsenic poisoning]] | |
| - | In an acidic medium, {{chem|As|3-}} is protonated to form [[arsine]] gas (AsH<sub>3</sub>), so adding sulfuric acid (H<sub>2</sub>SO<sub>4</sub>) to each side of the equation we get: | + | *[[Drug test]] |
| - | + | ||
| - | : As<sub>2</sub>O<sub>3</sub> + 6 Zn + 6 H<sup>+</sup> + 6 H<sub>2</sub>SO<sub>4</sub> → 2 As<sup>3−</sup> + 6 H<sub>2</sub>SO<sub>4</sub> + 6 Zn<sup>2+</sup> + 3 H<sub>2</sub>O | + | |
| - | + | ||
| - | As the As<sup>3−</sup> combines with the H<sup>+</sup> to form arsine: | + | |
| - | + | ||
| - | : As<sub>2</sub>O<sub>3</sub> + 6 Zn + 6 H<sup>+</sup> + 6 H<sub>2</sub>SO<sub>4</sub> → 2 AsH<sub>3</sub> + 6 ZnSO<sub>4</sub> + 3 H<sub>2</sub>O + 6 H<sup>+</sup> | + | |
| - | + | ||
| - | By eliminating the common ions: | + | |
| - | + | ||
| - | : As<sub>2</sub>O<sub>3</sub> + 6 Zn + 6 H<sub>2</sub>SO<sub>4</sub> → 2 AsH<sub>3</sub> + 6 ZnSO<sub>4</sub> + 3 H<sub>2</sub>O | + | |
| - | + | ||
| - | == First notable application == | + | |
| - | {{main|Marie LaFarge}} | + | |
| - | + | ||
| - | Although the Marsh test was efficacious, its first publicly documented use — in fact, the first time evidence from [[forensic toxicology]] was ever introduced — was in [[Tulle]], [[France]] in 1840 with the celebrated [[Marie LaFarge|LaFarge poisoning case]]. Charles LaFarge, a foundry owner, was suspected of being poisoned with arsenic by his wife Marie. The circumstantial evidence was great: it was shown that she brought arsenic trioxide from a local chemist, supposedly to kill rats which infested their home. In addition, their maid swore that she had mixed a white powder into his drink. Although the food was found to be positive for the poison using the old methods as well as the Marsh test, when the husband's body was exhumed and tested, the chemists assigned to the case were not able to detect arsenic. [[Mathieu Orfila]], the renowned [[toxicologist]] retained by the defense and an acknowledged authority of the Marsh test examined the results. He performed the test again and demonstrated that the Marsh test was not at fault for the misleading results but rather those who performed it did it incorrectly. Orfila thus proved the presence of arsenic in LaFarge's body using the test. As a result of this, Marie was found guilty and sentenced to life imprisonment. | + | |
| - | + | ||
| - | == Effects of the Marsh test == | + | |
| - | + | ||
| - | The case proved to be controversial, for it divided the country into factions who were convinced or otherwise of Mme. LaFarge's guilt; nevertheless, the impact of the Marsh test was great. The French press covered the trial and gave the test the publicity it needed to give the field of forensic toxicology the legitimacy it deserved, although in some ways it trivialized it: Marsh test assays were actually done in salons, public lectures and even in some plays that recreated the LaFarge case. | + | |
| - | + | ||
| - | The existence of the Marsh test also served a deterrent effect: deliberate arsenic poisonings became rarer because of the fear of discovery became more present. | + | |
| - | + | ||
| - | == See also == | + | |
| - | * [[James Marsh (chemist)|James Marsh]], who discovered the reaction in [[1836]] | + | |
| - | * [[Nascent hydrogen]] | + | |
| - | * [[Devarda's alloy]] | + | |
| - | * [[Arsine]] | + | |
| - | * [[Stibine]] | + | |
| {{GFDL}} | {{GFDL}} | ||
Current revision
|
Related e |
|
Featured: |
Forensic toxicology is the use of toxicology and other disciplines such as analytical chemistry, pharmacology and clinical chemistry to aid medical or legal investigation of death, poisoning, and drug use. The primary concern for forensic toxicology is not the legal outcome of the toxicological investigation or the technology utilised, but rather the obtaining and interpreting of the results. A toxicological analysis can be done to various kinds of samples.
A forensic toxicologist must consider the context of an investigation, in particular any physical symptoms recorded, and any evidence collected at a crime scene that may narrow the search, such as pill bottles, powders, trace residue, and any available chemicals. Provided with this information and samples with which to work, the forensic toxicologist must determine which toxic substances are present, in what concentrations, and the probable effect of those chemicals on the person.
Determining the substance ingested is often complicated by the body's natural processes (see ADME), as it is rare for a chemical to remain in its original form once in the body. For example: heroin is almost immediately metabolised into another substance and further to morphine, making detailed investigation into factors such as injection marks and chemical purity necessary to confirm diagnosis. The substance may also have been diluted by its dispersal through the body; while a pill or other regulated dose of a drug may have grams or milligrams of the active constituent, an individual sample under investigation may only contain micrograms or nanograms.
Contents |
Samples
Urine
A urine sample is urine that has come from the bladder and can be provided or taken post-mortem.
Blood
A blood sample of approximately Template:Convert is usually sufficient to screen and confirm most common toxic substances. A blood sample provides the toxicologist with a profile of the substance that the subject was influenced by at the time of collection; for this reason, it is the sample of choice for measuring blood alcohol content in drunk driving cases.
Hair sample
Hair is capable of recording medium to long-term or high dosage substance abuse. Chemicals in the bloodstream may be transferred to the growing hair and stored in the follicle, providing a rough timeline of drug intake events. Head hair grows at rate of approximately 1 to 1.5 cm a month, and so cross sections from different sections of the follicle can give estimates as to when a substance was ingested. Testing for drugs in hair is not standard throughout the population. The darker and coarser the hair the more drug that will be found in the hair.If two people consumed the same amount of drugs, the person with the darker and coarser hair will have more drug in their hair than the lighter haired person when tested. This raises issues of possible racial bias in substance tests with hair samples.
Oral fluid
Oral fluid is the proper term, however saliva is used commonly. Saliva is a component of oral fluid. Oral fluid is composed of many things and concentrations of drugs typically parallel to those found in blood. Sometimes referred to as ultra filtrate of blood, it is thought that drugs pass into oral fluid predominantly through a process known as passive diffusion. Drugs and pharmaceuticals that are highly protein bound in blood will have a lower concentration in oral fluid. The use of oral fluid is gaining importance in forensic toxicology for showing recent drug use, e.g. in clinical settings or investigation of driving under influence of substances.
Other
Other bodily fluids and organs may provide samples, particularly samples collected during an autopsy. A common autopsy sample is the gastric contents of the deceased, which can be useful for detecting undigested pills or liquids that were ingested prior to death. In highly decomposed bodies, traditional samples may no longer be available. The vitreous humour from the eye may be used, as the fibrous layer of the eyeball and the eye socket of the skull protects the sample from trauma and adulteration. Other common organs used for toxicology are the brain, liver, and spleen.
The inspection of the contents of the stomach must be part of every postmortem examination if possible because it may provide qualitative information concerning the nature of the last meal and the presence of abnormal constituents. Using it as a guide to the time of death, however, is theoretically unsound and presents many practical difficulties, although it may have limited applicability in some exceptional instances. Generally, using stomach contents as a guide to time of death involves an unacceptable degree of imprecision and is thus liable to mislead the investigator and the court. Characteristic cell types from food plants can be used to identify a victim's last meal; knowledge about which can be useful in determining the victim's whereabouts or actions prior to death (Bock and Norris, 1997). Some of these cell types include (Dickison, 2000):
- sclereids (pears)
- starch grains (potatoes and other tubers)
- raphide crystals (pineapple)
- druse crystals (citrus, beets, spinach)
- silica bodies (cereal grasses and bamboos)
In a case where a young woman had been stabbed to death, witnesses reported that she had eaten her last meal at a particular fast food restaurant. However, her stomach contents did not match the limited menu of the restaurant, leading investigators to conclude that she had eaten at some point after being seen in the restaurant. The investigation led to the apprehension of a man whom the victim knew, and with whom she had shared her actual final meal (Dickison, 2000). Time since death can be approximated by the state of digestion of the stomach contents. It normally takes at least a couple of hours for food to pass from the stomach to the small intestine; a meal still largely in the stomach implies death shortly after eating, while an empty or nearly-empty stomach suggests a longer time period between eating and death (Batten, 1995). However, there are numerous mitigating factors to take into account: the extent to which the food had been chewed, the amount of fat and protein present, physical activity undertaken by the victim prior to death, mood of the victim, physiological variation from person to person. All these factors affect the rate at which food passes through the digestive tract. Pathologists are generally hesitant to base a precise time of death on the evidence of stomach contents alone.
Other organisms
Bacteria, maggots and other organisms that may have ingested some of the subject matter may have also ingested any toxic substance within it.
Detection and Classification
Detection of drugs and pharmaceuticals in biological samples is usually done by an initial screening and then a confirmation of the compound(s), which may include a quantitation of the compound(s). The screening and confirmation are usually, but not necessarily, done with different analytical methods. Every analytical method used in forensic toxicology should be carefully tested by performing a validation of the method to ensure correct and indisputable results at all times. A testing laboratory involved in forensic toxicology should adhere to a quality programme to ensure the best possible results and safety of any individual.
The choice of method for testing is highly dependent on what kind of substance one expects to find and the material on which the testing is performed. Biological samples are more complex to analyze because of factors such as the matrix effect and the metabolism and conjugation of the target compounds.
Gas chromatography
Gas-liquid chromatography is of particular use in examining volatile organic compounds.
Detection of Metals
The compounds suspected of containing a metal are traditionally analyzed by the destruction of the organic matrix by chemical or thermal oxidation. This leaves the metal to be identified and quantified in the inorganic residue, and it can be detected using such methods as the Reinsch test, emission spectroscopy or X-ray diffraction. Unfortunately, while this identifies the metals present it removes the original compound, and so hinders efforts to determine what may have been ingested. The toxic effects of various metallic compounds can vary considerably.
Nonvolatile organic substances
Drugs, both prescribed and illicit, pesticides, natural products, pollutants and industrial compounds are some of the most common nonvolatile compounds encountered. Screening methods include thin-layer chromatography, gas-liquid chromatography and immunoassay. For complete legal identification, a second confirmatory test is usually also required. The trend today is to use liquid chromatography tandem mass spectrometry, predeced with sample workup as liquid-liquid extraction or solid phase extraction. Older methods include: spot test (see Pill testing), typically the Marquis Reagent, Mecke Reagent, and Froehde's reagent for opiates, Marquis Reagent and Simon's reagent for amphetamine, methamphetamine and other analogs, like MDMA, the Scott's test for cocaine, and the modified Duquenois reagent for marijuana and other cannabinoids. For compounds that don't have a common spot test, like benzodiazepines, another test may be used, typically mass spectrometry, or spectrophotometry.
See also
