Poisonous Tales
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A word shown in bold within the definition indicates another entry in the Glossary under that name. Chemical structures are generally shown above the entry text.
AAS or atomic absorption spectroscopy is a technique for detecting heavy metals. A liquid sample is turned into a very fine mist and set alight with a flame. Light is then passed through the sample and any metals present will absorb light of a specific wavelength, meaning they can be identified.
Acetylcholine is a neurotransmitter that acts on the nervous system to modulate (control) muscle movements. Drugs that interfere with its activity are called “anticholinergics”. Acetylcholine chloride is used clinically for cataract surgery.1
Aconitine is found in fresh aconite (wolfsbane or monkshood, Figure 5.1) plant material at concentrations ranging from 0.3–2%,2 with the highest concentrations found in the root. It is one of the three main alkaloids in the plant, alongside mesaconitine, and jesaconitine.
2-Aminothiazoline-4-carboxylic acid is a new marker for cyanide poisoning in post-mortem blood samples. It can be detected by LC-MS and is much more stable than cyanide itself.3
Amphetamine is a controlled stimulant drug (known as “speed”). It is used clinically in the UK to treat narcolepsy and ADHD.1
Amygdalin is a cyanogenic glycoside found in the stones or pips of plants of the Prunus species (see Figure 10.1 for an example). Levels in fruit are typically low: apricot (8%), plum (2.5%), bitter almond (5%) and peach (6%),4 but when eaten it is broken down by enzymes into hydrogen cyanide (HCN). The characteristic bitter almond taste comes from benzaldehyde, which is also made when the molecule breaks down.5 Amygdalin is sold as a nutritional supplement under the name “vitamin B17” to support the immune system.6
Apoatropine is an alkaloid that can be found in plants of the Solanaceae family, such as deadly nightshade (Figure 4.2). It is a dehydrated version of atropine because the two differ in their chemical structures by the presence of a water molecule.
Aspirin is an over-the-counter medication used to treat pain, inflammation and fever. It can also be used long term to prevent heart attack. Aspirin is made from salicylic acid, which was first extracted from the willow (Salix alba) tree (see Figure 3.6).7
Atropine is the main alkaloid found in deadly nightshade (Atropa belladonna) alongside hyoscine and scopolamine. 98% of the alkaloids present in the plant are atropine.8 The leaves contain 0.2–0.5% atropine,2,9 with the ripe berries containing around 0.6%.2 Atropine is prescribed in the UK as eye drops and for bradycardia (slower than normal heart beat).10
Brucine is found alongside strychnine in the seeds of the Strychnos nux-vomica (Figure 8.1) plant in approximately equal amounts.11 It is less toxic than strychnine,12 but is structurally very similar, differing only in two methoxy groups – giving it its alternative name of “dimethoxystrychnine”.
Bufadienolide is a cardiac glycoside found in some plants as well as in the skin of common toads (see Figure 6.4).
Captopril is a heart medication derived from the venom of the Brazilian arrowhead viper (Bothrops jararaca, Figure 9.6). It was used successfully to treat high blood pressure, but serious side-effects mean it is rarely prescribed now.13
Cardiac glycosides are alkaloids that affect the heart, and are found in plants such as digitalis (Figure 6.1). A “glycoside” is a chemical in which a type of sugar (shown in pink) is bound to the main molecule (black) via a “glycosidic” bond (green). In the case of cardiac glycosides, the molecule is similar to a steroid and contains a five-membered lactone ring (blue).14–16
Cerberin is a cardiac glycoside found in the kernel of the fruit of the pong–pong (Cerbera odollam) tree (see Figure 6.3). Ingesting half-to-a-whole kernel can be enough to cause death.17
Chloroform, also known as “trichloromethane”, is a liquid that evaporates into a gas very quickly. It was used in the past as an anaesthetic for operations, but is now mainly an industrial solvent. Although fiction suggests that the merest whiff of a handkerchief soaked in chloroform would be enough to incapacitate a would-be victim, in reality 5 min or more was needed to produce anaesthesia (in a willing patient, never mind someone struggling).18
Chlorpromazine is a prescription antipsychotic medication. It can also be used to treat nausea and vomiting.1
Cholestyramine, also known as “colestyramine”, is used to treat high cholesterol. It binds to bile acids (the precursors of cholesterol) that have been digested, preventing them from being re-absorbed into the body.1 It can be used to treat digoxin poisoning as it binds to digoxin molecules, preventing them from being reabsorbed and speeding up their elimination from the body.19
Cicutoxin is a drug long-chain highly unsaturated alcohol found in several plant species including water hemlock (Cicuta maculate, Figure 3.4). The roots of the water hemlock plant contain approximately 3–5% cicutoxin.20
Cocaine is a controlled stimulant drug used recreationally for it euphoric effects. Powder cocaine (cocaine hydrochloride) is snorted or injected, whereas crack cocaine (cocaine free base) is smoked. It is often adulterated with anaesthetics such as lidocaine. It is no longer used clinically in the UK. It is found in the coca leaf (Erythroxylum coca) plant.
Codeine is an opiate found naturally in opium poppies (Figure 2.1), making up around 0.5–1% of raw opium depending on soil and climate.2,21 When used clinically, it is usually prescribed for mild-to-moderate pain in the form of the phosphate salt, and can be given as tablets or by injection.1 Codeine rapidly converts to morphine in the body.
Conhydrine is a piperidine alkaloid found in the hemlock (Conium maculatum, Figure 3.3) plant.22
Coniine (also known as “cicutine” or “conicine”) is a piperidine alkaloid found in the hemlock (Conium maculatum) plant with the plant’s fruits, stems and leaves containing 0.1–2% coniine.23,24 Like many alkaloids, coniine can occur in two optically active forms, and it is the (R) form that is naturally occurring.25 It is not used clinically in the UK.1 Coniine was the first alkaloid structure to be fully resolved.22
Cyanogenic glycosides are alkaloids containing one or two sugars connected to a molecule containing a C≡N group via a glycosidic linkage.4 They can produce hydrogen cyanide (HCN) when eaten. An example is linamarin (shown), which is found in plants such as raw cassava. Cassava can be eaten safely by first grinding it into flour and then soaking in water, during which the HCN evaporates.26
Derivatisation involves reacting one drug with another to make a slightly modified version, known as a “derivative”. This is needed for some drugs because they are unstable at the high temperatures used in GC-MS. In the example shown, methamphetamine is reacted with the derivatising agent TFAA. The bulkier derivative can withstand higher temperatures.
Diazepam is a controlled drug, commonly known as Valium. It belongs to a family of drugs known as “benzodiazepines”. Diazepam is prescribed for muscle spasms, such as sciatica, anxiety and insomnia.1
Dictamnine is an alkaloid found in the root bark of the dittany (Dictamnus albus) plant. It is used to treat jaundice but can cause a rash if it comes into contact with the skin.27
Digitoxigenin is found alongside other cardiac glycosides such as oleandrin in common oleander (Nerium oleander, Figure 7.1) plants.28
Digitoxin is found alongside other cardiac glycosides such as digoxin in digitalis (foxglove) plants. It is also converted into digoxin by the body. Digitalis plants contain up to 0.4% digitoxin.24 Digitoxin can be used clinically to treat congestive heart failure but is not prescribed in the UK.1
Digoxin is found alongside other cardiac glycosides such as digitoxin in digitalis (foxglove) plants. Digitalis plants contain 0.5–1.5% cardiac glycosides including digoxin.11 It is also prescribed to correct irregular heartbeat.
Dimercaprol is an antidote to heavy metal poisoning such as mercury. Metals binds to the S atoms and are carried out of the body through the urine.29
3,5-Dimethoxyphenol is formed from taxicatine when the bond connected to the sugar molecule (the glycosidic bond) is broken.30 The part of the molecule remaining when this happens is known as an “aglycone”.31,32
Dimethylsulfoxide or DMSO is a solvent (a liquid used to dissolve other liquids) that allows drugs to be absorbed through the skin. It is also used to treat inflammation and cystitis.24 More recently it has been found to protect cells when they are frozen at very low temperatures in cryogenics.
Diphenhydramine is an antihistamine used as an over-the-counter sedative or hypnotic (sleeping tablet) under brand names such as Nytol®.
Docetaxel is sold under the brand name Taxotere®. It is a semisynthetic chemotherapy agent derived from the yew tree (Taxus baccata, Figure 3.5). It is prescribed in the UK to treat breast cancer.1
Echinacoside is found in Echinacea (Figure 9.4) plants, and is an established herbal remedy sold as teabags or in tablets. It is most often used to treat cold and flu symptoms, and the roots of plants can contain 0.3–1.0% echinacoside.33 It has also been used as a traditional remedy for snake bite envenomation.
Eleutheroside is an alkaloid found in the roots of Eleutherococcus senticosus plants. It is commonly sold in ginseng supplements.
Enzymes are active proteins that cells use to transform other molecules e.g., to turn a parent drug into a metabolite. They are natural catalysts inside the body, but are also used in things like biological washing powder.34
Epicatechin is a flavanol (a kind of plant nutrient rather than a poison) found in many different fruits. It has anti-oxidant properties and is sold as a supplement.
Fluorescence happens when molecules absorb light of a certain wavelength then emit the light at a different one in the form of a glow. The wavelength of the glow is often highly specific to a drug or poison (e.g., LSD) and can be measured and used to detect it.
Galanthamine also known as “galantamine”, is found in bulbs of the snowdrop (Galanthus nivalis, Figure 2.5) plant but is also produced synthetically and used clinically as a prescription medication for mild-to-moderate dementia in Alzheimer’s disease.1
γ-Coniceine is a piperidine alkaloid found in the leaves and young tissues of the hemlock plant (Conium maculatum).22 Hemlock can contain up to 3.5% piperidine alkaloids including N-methylconiine, coniine and γ-coniceine.2
GC-MS or gas chromatography-mass spectrometry is a separation and identification technique combining gas chromatography and mass spectrometry. In the first step, a mixture is heated to a high temperature (>100 °C) and carried through a column under pressure by an unreactive gas such as helium. During this process, any molecules of interest (“analytes”) separate out and exit the column at different times. The separation process is guided by the lining of the column (known as the “stationary phase”), which can be made of different types of chemicals. In the second phase, as the analytes leave the column they enter the mass spectrometer and are given an electrical charge. The charged versions (ions) are then broken down into small pieces (fragments) each of which is represented by a number (the mass-to-charge ratio or m/z). Each molecule breaks down in a unique way to produce a pattern or “spectrum”. The analyte can then be identified by comparing the spectrum to a known sample of the drug or poison (either by running the known sample through the same GC-MS or using a library of spectra). GC-MS requires some sample preparation e.g., extraction before body fluid samples such as blood or urine can be analysed. Some drugs, such as amphetamine may need to be chemically modified further (derivatised) to protect them from the high temperatures in the instrument.
GC–NPD or gas chromatography with nitrogen–phosphorus detection This combines the gas chromatography described above with a detector for nitrogen and phosphorous atoms. The sample is burned in a flame to produce ions, which can be measured as an electric current.
Glycine is an amino acid. Its role in the body is as a neurotransmitter (chemical messenger) that slows down and controls the activity of muscles. Poisons such as strychnine affect glycine, leading to muscles becoming overstimulated.
Heroin is also known as “diacetylmorphine” or “diamorphine” and is produced by acetylating the morphine found in raw opium. Although diamorphine is occasionally still used in emergency medicine for acute pain,1 it is now much more likely to be seen by forensic toxicologists as a drug of abuse. The term “heroin” in the UK refers to the (usually) powdered mixture of diacetylmorphine and the various cutting agents used to improve profitability. Diacetylmorphine rapidly converts to morphine in the body. As illicit heroin usually contains some acetylated codeine, codeine itself is often also found in toxicology cases involving heroin users.35
HPLC-DAD or high-performance liquid chromatography with diode array detection is a separation and identification technique. A liquid sample (a mixture) is forced down a column under pressure by a liquid mobile phase (usually a mix of buffers and organic solvents).36 During this process, any molecules of interest separate out and exit the column at different times. The separation process depends on what is inside the column (known as the “stationary phase”). As the individual chemicals in the mixture emerge from the column they pass into a detector. The most common type of detector used with HPLC is an ultraviolet-visible or diode array detector. These shine light of different wavelengths through each of the analytes in the mixture. Each one will absorb light at a slightly different characteristic wavelength, allowing them to be identified by comparison with a known sample or reference books. Whilst a standard ultraviolet-visible detector uses one wavelength at a time, a DAD uses multiple wavelengths.
Hydrastine is found in goldenseal (Hydrastis canadensis, Figure 8.3) and has similar effects to strychnine. It can poison people drinking herbal teas.
Hyoscyamine, also known as “daturine” occurs naturally in the henbane (Hyoscyamus niger, Figure 3.1) plant. When attempts are made to isolate it from the plant some hyoscyamine is converted into its optical isomer (mirror image), known as atropine.37 All parts of the plant contain hyoscyamine,38 with content increasing from the root (0.08%) to the leaves (0.17%) and seeds (0.3%).2 Clinically, hyoscyamine sulfate has been used to control gastrointestinal tract problems11,39 but it is no longer prescribed in the UK.1
Hypaconitine is found in the aconite (wolfsbane or monkshood) plant. It is more potent than both aconitine and mesaconitine.40
Immunoassay, is based on antibody–antigen binding. In forensic toxicology, the antigen is the drug or poison being targeted during the test. In a typical immunoassay used in toxicology, a small amount of the sample is added to a well that has been coated with a specific antibody (e.g., morphine antibodies for an opiates immunoassay). If there is any antigen in the sample, the antibodies sitting in the well will recognise it and bind to it. Normally, this binding cannot be seen by eye, so a colour change is used to show how much (if any) antigen was present in the sample. The amount (or intensity) of the colour can be measured and converted to a number. Somewhat counter-intuitively, the more intense the colour, the higher the number, and the lower the amount of drug or poison present in the sample. A low-intensity result indicates that one or more members of a drug ‘family’ are present. Immunoassays require very little sample preparation, but are classed as presumptive tests and positive results must be confirmed by a more specific technique such as LC-MS or GC-MS before they can be used in Court.
Jesaconitine is found in the aconite (wolfsbane or monkshood) plant. It is one of the three main alkaloids in the plant, alongside aconitine, and mesaconitine.
Lactate is created by muscles during metabolism (burning of glucose). Normally it is removed from the body, but some diseases and strychnine poisoning can cause it to build up, eventually lowering the pH of the blood to dangerous levels.
Laetrile is an alternative cancer cure. Products sold as ‘laetrile’ can contain amygdalin, mandelonitrile (upper structure) or d-mandelonitrile-β-glucuronide (lower structure). All three compounds are related by metabolism. Laetrile is a controversial drug having yet to be proved effective, and also associated with several poisonings.
LC-MS or liquid chromatography-mass spectrometry is a separation and identification technique combining HPLC and mass spectrometry. As the analytes leave the HPLC column they enter the mass spectrometer and are given an electrical charge. The ions are then broken down into fragments, each of which is represented by its mass-to-charge ratio (m/z). The fragments then break down further via a “transition” that is characteristic to that molecule. For example, cocaine has a characteristic transition where an ion with a number of 304 breaks down into a smaller ion of number 182, plus some very small background ions (the transition is represented as: 304 → 182).41 These transitions are monitored and compared to the behaviour of a known sample of the drug or poison. In some testing, two mass spectrometers are used, known as tandem mass spectrometry (LC-MS/MS). Using two mass spectrometers means the small background ions can be filtered out by the first instrument, making the technique more sensitive. LC-MS requires some sample preparation e.g., extraction before body fluid samples such as blood or urine can be analysed.
Lidocaine is a local anaesthetic and usually applied to the skin as a gel or cream. It can also be used during cardiopulmonary resuscitation (CPR), when it is injected.1 It has a similar numbing effect to cocaine, so is sometimes seen as a cutting agent in street cocaine samples.42
Linamarin: see cyanogenic glycosides.
LLE or liquid–liquid extraction is a sample clean-up method that uses two immiscible layers (one watery such as urine or blood, and one of organic solvent) to draw drugs and poisons out of a biological sample. To move from the blood or urine into the solvent, the drugs must be uncharged (no +ve or −ve charges on the molecule) so often a change in pH is needed as a first step. For drugs containing nitrogen (e.g., most alkaloids) the sample has to be made more alkaline. Then the organic solvent is added, and this forms a layer on top of the watery sample. Although the two layers never truly mix, by shaking, stirring or vortexing, an exchange of drugs between the two can happen. After centrifuging (spinning at high speed) the organic layer is removed then injected into the GC-MS or LC-MS instrument.
Mesaconitine is found in the aconite (wolfsbane or monkshood) plant. It is similar to aconitine in terms of toxicity.40
Methamphetamine is a controlled stimulant drug. Crystals of methamphetamine hydrochloride (known as “crystal meth”) are usually inhaled. It is not used clinically in the UK, but in other countries may be used as a prescription drug to treat ADHD.
Methaqualone is a sedative hypnotic that was used clinically and was also a drug of abuse. It has also been found as an adulterant in heroin.42 It is no longer used clinically in the UK.
Morphine is the main opiate found naturally in the opium poppy, making up around 10–15% of raw opium depending on soil and climate.2,21 When used clinically, it is usually prescribed for moderate-to-severe pain and in palliative care in the form of the sulfate or hydrochloride salt,43 and can be given as tablets, injection or an oral solution.1
Naloxone is a widely used antidote to opioid overdose. It can be given as a naloxone hydrochloride injection or in a nasal spray, and reverses the respiratory depression effects of opioids such as heroin.
Neriine (also known as “conessine”) is a cardiac glycoside found in all parts of the oleander (Nerium oleander) plant.44
Nicotine is a piperidine alkaloid found in the tobacco (Nicotiana) plant. It is a stimulant and highly addictive. The amount of nicotine in the leaves of the tobacco plant varies widely from 0.3–7%.45
NMDA, N-Methyl-d-aspartate or N-methyl-d-aspartic acid is chemically related to amino acids and binds to NMDA receptors in nerve cells. These receptors are important for controlling memory function.
N-Methylconiine also known as “N-methyl coniine” or “methylconiine”, is a piperidine alkaloid found in the fruits of the hemlock (Conium maculatum) plant. Hemlock can contain up to 3.5% piperidine alkaloids including N-methylconiine, coniine and γ-coniceine.2
Oenanthotoxin, also known as enanthotoxin is found in the hemlock water dropwort (Oenanthe crocata) plant, one of the two known as “dead men’s fingers”.2 It causes severe convulsions and is related to cicutoxin.46
Oleandrin (upper structure), found in Nerium oleander plants, breaks down into oleandrigenin (lower structure) by losing a sugar molecule (known as “deglycosylation”). Leaves from Nerium oleander were shown to contain 0.018 to 0.425% of the cardiac glycoside oleandrin.28 Although all parts of the plant are poisonous, the highest concentration of oleandrin is found in the root.47 The structure is similar to naturally occurring and synthetic steroids.
Oxalic acid is found in rhubarb (Rheum rhabarbarum) plants. Although the stalks of the plant are safe to eat, the leaves can cause vomiting and convulsions.
Physostigmine is found in the Calabar bean (Physostigma venenosum) plant and is also used as a prescription medicine for glaucoma.48 It can be used to treat poisoning by substances that interfere with the transmission of acetylcholine such as atropine and scopolamine.
Pilocarpine is an eye medication for glaucoma and an antidote to atropine poisoning.49 It has the effect of shrinking the pupils (miosis), reducing the pressure inside the eye, and can also be used for treating a dry mouth. It is an alkaloid extracted from the Pilocarpus plant and mimics the actions of acetylcholine.48
Piperidine alkaloids are chemicals with a six-membered carbon ring where one carbon has been replaced by a nitrogen.22 They include nicotine, and coniine.
Polyurethanes are plastic polymers that produce hydrogen cyanide (HCN) and carbon monoxide (CO) when burned.50 They are commonly used to make foams, but when used in soft furnishings must be treated with a flame retardant.
Protoanemonin is one of the veratrum alkaloids found in the hellebore (Veratrum, Figure 5.2) plant. It causes vomiting, muscle twitching and convulsions. Hellebore roots contain about 0.01% veratrum alkaloids.2
Protopine is a toxic alkaloid found in bleeding heart (Dicentra spectabilis or Lamprocapnos spectabilis, Figure 7.5) plants.51 Overall alkaloid content in the plant is <0.7%.4 It has recently been investigated as a cholesterol-lowering drug.52
Putrescine is produced when amino acids are broken down. As this typically happens when an organism dies it is responsible for the bad smell of decomposing flesh.
Quercetin is a flavanoid (not an alkaloid because it doesn’t contain nitrogen) found in many vegetables and fruits with potentially beneficial health benefits. It can be used as a folk remedy for snake bite envenomation.
Quinidine (upper structure) is a stereoisomer of quinine (lower structure), which was originally derived from the bark of the cinchona tree to treat malaria.53 It is used clinically to restore normal heart rhythms. The alkaloid content of Cinchona ledgeriana is 5–8%, of which three-quarters is quinine.27 Quinidine is present in the bark at a concentration of 0.25–3%.24
Retronecine is an alkaloid found in common comfrey (Symphytum officinale). Overall alkaloid content in the plant is 0.02–0.29%. The plant can be made into a herbal tea, taken for aches and pains, applied to the skin for wound healing, or stewed to use as a garden fertilizer. Ingesting the plant is now not advised, as retronecine is thought to be toxic.4,44
Salicylate, also known as “salicylic acid” is found in the bark and leaves of willow trees (Salix alba) and was used for aches and pains.53 It is also a breakdown product of aspirin and a common ingredient in anti-acne products.
Scopolamine, also known as “l-hyoscine”, is one of the alkaloids found in the mandrake (Mandragora, Figure 2.2) and jimsonweed (Datura, Figure 7.3) plants, making up 0.4% of the mandrake root.54,55 It is used clinically as hyoscine butylbromide for irritable bowel syndrome, and as hyoscine hydrobromide for motion sickness.1
Selegiline (sold as Eldepryl® in the UK) is used to treat Parkinson’s disease. It breaks down in the body into the controlled drugs amphetamine and methamphetamine.56
Sensitisation means that every time a dose of a drug or poison is taken, the user experiences a stronger effect. It is the opposite of tolerance. Sensitisation is a reaction of the immune system and in rare cases can lead to serious anaphylaxis.
Solanine is the major active ingredient in the woody nightshade (Solanum dulcamara, Figure 4.4) plant and is also found in green (unripe) potatoes.57 It is poisonous, but victims show different symptoms to deadly nightshade poisoning with the most common being stomach pain, nausea, vomiting and diarrhoea. Plants can contain up to 6.1% solanine.4 Solanine has a similar chemical structure to steroids and also to cardiac glycosides such as digoxin and digitoxin.
SPE or solid-phase extraction is a type of clean-up method that is applied to samples such as blood and urine in forensic toxicology. The liquid samples are sucked through a small cartridge containing a permeable ‘bed’ using a vacuum. Depending on the target drug or poison, the bed can be made of different chemicals. It initially traps the chemical of interest whilst allowing others to pass through, cleaning up the sample. Finally, a solvent is drawn through the cartridge, which carries the analyte over the bed.
Spectrophotometry is a technique used to detect carboxyhaemoglobin (COHb) in blood. COHb is produced when we breathe in carbon monoxide and the % saturation of the blood usually correlates with the severity of the poisoning. Spectrophotometry works by shining light of different wavelengths through the sample and monitoring how much is absorbed. The amount absorbed and the wavelengths are characteristic to COHb and can be used to create a picture or “spectrum”.
Strychnine is found in the seeds of the Strychnos nux-vomica plant (seeds contain 1–1.4% strychnine).58 Although it was isolated from the plant in the 1800s, its chemical structure was disputed for years and not confirmed until 1952.59
Taxicatine, also known as “taxicatin” is an alkaloid found in yew (Taxus baccata). It is a cardiac glycoside.
Taxines are the major active compounds of yew (Taxus baccata) and are found at 0.1–1% in the needles. Taxine A (above) comprises approximately 1.3% of the total alkaloid content in yew.60
Taxine B has two isomers: taxine B (above) and isotaxine B (below).61,62 They are the main alkaloids in yew needles, and levels in the plant vary seasonally, with the highest concentration of taxines found in January (1.2% dry weight in the needles).30 The taxine B isomers comprise approximately 30% of the total alkaloid content.60 It is not known which of taxine B or isotaxine B is more toxic.61 The chemical structures of taxines are similar to the alkaloids found in digitalis, which may lead to false-positive results during digoxin testing (see Chapter 6).
Thebaine is an opiate found naturally in opium, making up around 0.2–0.5% of raw opium depending on soil and climate.2,21 It is not used clinically in the UK.
Thevetin A is found in the seeds of the yellow oleander (Thevetia peruviana, Figure 7.2) plant. It is a cardiac glycoside.4
TOF-MS or time-of-flight mass spectrometry is a type of detector used in LC-MS. It works by creating ions, firing them down a long tube and timing how long they take to reach the end. Larger ions are slower than smaller ones, although even the slowest take only a fraction of a second. The time taken is characteristic to the mass of the ion and this can be compared to a library.
Tolerance is an effect that long-term users of certain drugs experience, whereby they need to take increasingly higher doses to achieve the same effects. These may be pleasurable or medical effects e.g., pain relief. Tolerance is commonly seen for opiates and alcohol. It can occur because the body becomes more efficient at eliminating the drug from the body (“metabolic tolerance”), or because the user becomes used to the effects (“behavioural tolerance”).