Tracking Illicit Drugs with Strontium Isotope Analysis

Tracking Illicit Drugs with Strontium Isotope Analysis

The manufacture and distribution of illicit drugs such as heroin is a primary focus of many major law enforcement organisations worldwide, including the Drug Enforcement Agency (DEA) in the United States and the National Crime Agency (NCA) in the United Kingdom. Unfortunately, as drug shipments pass hands between dealers and cross borders so rapidly, it can be difficult if not impossible to trace a batch of drugs back to an initial manufacturer. As a result of this, the chances of locating and arresting the manufacturers of illicit drugs can be slim.

To a forensic drugs analyst, a whole range of characteristics can be examined and used to classify and compare different batches of the same drug, including physical appearance, packaging, and chemical composition. To an extent, heroin chemical signatures are already beneficial in comparing different batches of the drug in attempts to establish links and possible sources of the narcotics. This may be based on agents or adulterants a product has been cut with, and the relative concentrations of those substances. The manufacturing process itself can vary in terms of chemicals and apparatus used and the skills of the manufacturer, resulting in further characteristic differences in the chemical profile. However these differences may not be distinct enough to be valuable and are certainly not able to pinpoint the country from which a batch originated. Though there is still no reliable method of tracing an illicit drug back to a particular location, ongoing research is aiming to change this.

One method of studying the history and even origin of a sample is to use isotopic composition. Isotopes are different forms of elements that are incorporated into substances in the environment in varying ratios and abundances, influenced by a number of factors that can alter these ratios. These processes can be described as isotopic fractionation. Interestingly, isotopic ratios can be characteristic to different regions of the world, enabling certain materials to be traced back to the geographic region based on the ratios of particular isotopes contained within that material. With this in mind, they have often been used to trace unidentified human remains to a particular location or study the origin of food products. Focusing on isotopes allows for heroin samples to be studied and compared based on regional characteristics as oppose to the variation caused by the production process.

For the first time, researchers at Florida International University have utilised strontium isotope ratio analysis to determine the provenance of illicit heroin samples. 186 unadulterated, undiluted heroin samples of known origin were obtained from a number of geographic regions including Southeast Asia, Southwest Asia, South America, and Mexico. Of a particularly challenging nature is South American heroin and SA-like Mexican heroin, which can be extremely difficult to differentiate based on their chemical compositions alone. Heroin samples were dissolved via a microwave-assisted acid digestion method before being subjected to a technique known as a multi-collector inductively-coupled plasma mass spectrometry (MC-ICP-MS). This instrument utilises an inductively coupled plasma ion source to ionise target analytes, which are then separated and analysed by the mass spectrometer. The use of MC-ICP-MS allows for the strontium concentration of particular samples to be determined. The strontium isotope ratio (87Sr/86Sr) value of each individual sample was then compared with the overall mean values of ratios from different regions in order to establish the likely origin of that particular heroin sample. Samples from the same geographic region would be expected to exhibit a similar isotope ratio.


Multi-collector inductively-coupled plasma mass spectrometer (MC-ICP-MS) Source:

The results demonstrated the possibility of differentiating between heroin of different geographic origin. South American and Mexican heroin samples were correctly classified 82% and 77% of the time respectively. South East and South West Asian heroin samples were somewhat more difficult to differentiate due to more of an overlap between strontium isotope ratio values. SE Asian samples were correctly classified 63% of the time and SW Asian samples only 56% of the time. It is not clear whether this elemental strontium is endogenous or the result of external contamination, but either way it is sufficiently characteristic to be associated with a particular geographic location.

The strontium isotope composition of heroin can be affected by a number of factors, including the soil in which components are grown and groundwater in the area, which can result in region-specific isotope compositions. The use of strontium isotope ratio analysis has presented promising results in the origin determination of illicit heroin. Although a larger scale study incorporating samples of a more worldwide origin would be ideal, initial results suggest that this technique could allow for an unknown illicit drug sample to be traced back to a country of origin, aiding criminal intelligence agencies in the war against drugs.


Debord, J., Pourmand, A., Jantzi, S., Panicker, S. & Almirall, J. Profiling of Heroin and Assignment of Provenance by 87Sr/86Sr Isotope Ratio Analysis. Inorg Chim Acta. In press (2017).

Keeping the Skies Safe with Analytical Chemistry

Ever since events such as 9/11, the Lockerbie bombing and the (fortunately) failed shoe bomber, the stringency of airport security has been ever increasing. Anyone who has passed through an airport has no doubt witnessed the occasional swabbing of luggage or electronic items. The staff will take a quick swab of the item, stick it into a mysterious machine and usually send the passenger on their way with little explanation of what has just occurred.

But what exactly are they testing for in this scenario, and just what is the instrument they’re using?

As one might expect, the biggest target of this security step is explosive substances as a counter-terrorism measure, in addition to illicit narcotics in an attempt to crack down on drug trafficking. In an airport setting, the analytical testing technique of choice is ion mobility spectrometry.

Ion mobility spectrometry (IMS) is an analytical technique used to identify chemical compounds based on the differences in the movement of ions under an electric field. The concept for the technique was established in the early twentieth century, however it was not until the 1970s that the instrumentation was actually properly developed. There are currently tens of thousands of IMS devices deployed around the world. Not only are they utilised in airports for drug and explosives screening, but also by the military for the detection of chemical warfare agents and in industrial settings to monitor air quality. The range of applications is potentially vast, but the principles of operation are the same.

As you may have witnessed, a small swab is rubbed over the surface to be tested, typically a piece of luggage or an electronic device such as a laptop, before being inserted into the ion mobility spectrometer. As the sample needs to be introduced in its gaseous form, the swab may be subjected to heating in order to thermally desorb analytes from the swab and allow them to be transported into the instrument for analysis. In order to manipulate the analytes entering the instrument, they must first be converted into ions, their charged form. Ionisation is typically achieved using a radioactive source, such as 63Ni (nickel-63) or 241Am (Americium-241), which first form reactant ion species from the carrier gas (usually air), which then leads to the ionisation of the sample material. These newly-formed ions will then enter a region under an electric field and drift towards a series of electrodes. The ions will pass through the drift region at different speeds depending on the shape and size of the ion clusters and strike the electrodes, the signals being amplified and detected. Depending on the instrument and needs of the analysis, either positive or negative ions will be produced (in some cases both simultaneously).


IMS schematic. Source: Smiths Detection (

The IMS utilised in airports will typically hold a database of known explosive and narcotic substances against which to compare samples. There will be a certain threshold, typically based on peak intensity, that must be reached before a positive identification will be indicated, and if there is a “match”, the operator will be alerted to a potential identification.

In comparison to other analytical tools available, ion mobility spectrometers are far from being the best. For instance mass spectrometry, an alternative technique for the analysis and identification of chemical compounds, can offer greater sensitivity, higher resolution, improved accuracy and better identification. So why use IMS? It essentially comes down to cost and ease of use. The simple design and ability to operate at atmospheric pressure means the instruments can be fairly small in size, some even being hand-held and so rendering them completely portable. They have low power consumption, so can simply be powered by a few AA batteries. The ease of use of the IMS means anyone can be trained to use the instrument, thus technical or scientific expertise is not required.

But what is perhaps most important for use in an airport setting with potentially thousands of passengers each hour, is the ability to conduct analyses quickly, and this is something that the IMS can offer. Many commercial ion mobility-based instruments can provide results in a matter of seconds. For instance, the IONSCAN by Barringer (now owned by Smiths Detection) boasts the ability to detect over 40 explosives and narcotics in just 8 seconds.

In a security setting there are three primary types of IMS that may be encountered. The smallest of the devices are handheld and sample by drawing in analytes present in the atmosphere. These may be used to analyse potential hazards relating to unattended baggage, for example. The second type, which is perhaps the most commonly encountered IMS in airports, is a benchtop instrument which requires introduction of the sample via some type of swab. And finally, some airport security units may utilise a larger, human-sized IMS portal. This setup uses airflow to dislodge particles of explosives or drugs from clothing or the passenger’s body and analyse them.

Unsurprisingly, the instruments are not infallible, and false positive or negative results are a possibility. Some ions will have the same drift time so may be indistinguishable from known explosives or drugs, triggering an alarm. In actual fact this response may simply have been caused by a cosmetic or pharmaceutical product that happens to produce a response similar to a known narcotic. On the contrary, dirt, oil and other contaminants may mask the presence of substances of interest, thus causing no alert despite the presence of a drug or explosive.

Furthermore, the IMS is somewhat limited in that it can only identify the presence of a compound contained within its database. So whereas it may be able to detect common explosives such as RDX, TNT and PETN, and frequently encountered narcotics such as cocaine, heroin and cannabis, it would not necessarily alert to the presence of an unknown compound (unless it was very similar in chemical structure to something in the database).

Fortunately research in the field of analytical chemistry is constantly ongoing, aiming to improve instrumentation and analytical techniques to resolve these issues and ultimately produce more reliable and robust security measures.



G. Ewing et al. A critical review of ion mobility spectrometry for the detection of explosive and explosive related compounds. Talanta. 54 (2001) 515-529.

Homeland Security Science & Technology. IMS-Based Trace Explosives Detectors for First Responders. [online] Available:

Smiths Detection. Ion Mobility Spectrometry (IMS). [online] Available:

VX and Other Deadly Nerve Agents

It has now been confirmed that Kim Jong-nam, the half-brother of North Korean Leader Kim Jong-un, may have been assassinated using a highly toxic nerve agent known as VX. The attack occurred last week (13th February) in Kuala Lumpur airport, suspected to have been committed by two women who reportedly sprayed the chemical into his face before fleeing the scene.

VX, or S-[2-(Diisopropylamino)ethyl] methylphosphonothioate, is a nerve agent initially developed at the Porton Down Chemical Weapons Research Centre in Wiltshire, UK in 1952. Having originally been the focus of research elsewhere into the development of new organophosphate compounds as pesticides, the British military soon established an interest in the compound and continued its development.


S-[2-(diisopropylamino)ethyl] methylphosphonothioate) or VX

Typically encountered in liquid form, this clear or sometimes amber-coloured, oily substance is notoriously difficult to detect, lacking in both taste and odour. Its toxicity makes it one of the deadliest chemical warfare agents, requiring as little as 10mg adsorbed through the skin to be fatal. Its deadliness is only further increased by the persistence of the agent, making it difficult to decontaminate people and areas tainted with the chemical.


The mechanism of action of VX is identical to many similar nerve agents. The compound can enter the body by a range of potential routes, including ingestion, inhalation or skin contact. Once inside the body, VX inhibits the function of acetylcholinesterase (AChE), an enzyme responsible for catalysing the breakdown of acetylcholine. Acetylcholine is released over a synapse following an electric nerve impulse, ultimately resulting in a muscle contraction. However when VX binds to the active site of acetylcholinesterase, it renders the enzyme inactive, thus preventing it from breaking down the acetylcholine. As the nervous system is flooded with excess acetylcholine,  repeated muscle contractions occur, eventually resulting in asphyxiation due to constant contraction of the diaphragm muscle.

The effects of VX will typically occur immediately after exposure, beginning with coughing, shortness of breath and a tightness in the chest. A headache and blurred vision soon follows, along with symptoms such as vomiting, diarrhoea and abdominal pains. Given a sufficient dose, seizures will then occur as the drug attacks the nervous system, eventually resulting in a coma and asphyxiation.

If administered promptly, there are antidotes for VX. Atropine, typically administered by injection, is an anti-nerve agent that blocks the acetylcholine receptors, alleviating the symptoms brought on by the nerve agent. However it is worth noting that compounds such as atropine are toxic in their own right and, although they may save the person’s life by alleviating the effects of the nerve agent, they will still have an adverse effect on the patient. In addition to this, pralidoxime (or 2-PAM), can be administered to reactivate the enzyme, thus reversing the effects of VX. 2-PAM is a safer compound to use than atropine, but its effects are much slower.

Other Nerve Agents

VX is just one of many known toxic nerve agents. Nerve agents can typically be classed as either G-series or V-series. G-series agents were first synthesised by German scientists during World War II, and include tabun (GA), sarin (GB), soman (GD), and cyclosarin (GF). The first compound to be discovered, tabun, was accidentally synthesised by Dr Gebhardt Schraeder, who was investigating the development of organophosphate-based pesticides. The German army soon realised the potential use of such compounds, and went on to fund the development of other nerve agents such as sarin. The G-series chemicals are all clear, colourless liquids at room temperature, but are largely utilised as gases due to their high volatility.

The V-series nerve agents, which include VX, VE, VG, VM and VR, were developed a few years later, initially in the UK but some later in Russia. Unlike the G-series compounds, V-agents are very persistent and are not easily washed away or degraded, meaning they can remain on surfaces for long periods of time.

Fortunately the V-series nerve agents have generally not been exploited outside of military research, and the death of Kim Jong-nam may well be the first known use of the toxic agent in an assassination. However the G-series have received a great deal of malicious use and attention over the years, ranging from the Tokyo sarin subway attack in 1995 to its recent use in the Syrian civil war

VX, along with numerous other toxic nerve agents, were banned under the Chemical Weapons Convention of 1993, rendering the manufacture, possession and use of such substances illegal.



BBC News. VX nerve agent: The chemical that may have killed Kim Jong-nam. [online] Available:

University of Bristol Chemistry on the Screen. VX Nerve Gas. [online] Available:






Sex Determination with Raman Spectroscopy

Sex Determination with Raman Spectroscopy

The ability to quickly identify a victim or suspect during a criminal investigation is crucial, and the use of fingerprinting and DNA profiling often proves invaluable in this. However, a fingerprint or DNA profile can only be associated with an individual if there is an alternative profile or database match for comparison.

But what can investigators do when comparison profiles are not available, rendering biological fluids found at crime scenes somewhat useless?

The capability of instantly establishing alternative information relating to a suspect – such as sex, age or a phenotypic characteristic – based on the analysis of the evidence could be a substantial benefit to an investigation.

In recent years, the use of both well-established and novel analytical techniques to ascertain information relating to a suspect or victim from bodily fluids has been the focus of a great deal of research. With an increasing number of analytical instruments becoming field portable, the possibility of in situ analysis at crime scenes and instant suspect information is quickly becoming a reality.

Raman Spectroscopy and Sex Determination

Most recently, researchers at the University of Albany (Muro et al, 2016) have highlighted the possibility of using portable Raman Spectroscopy to determine the sex of an individual based only on their saliva in real-time.

The study utilised a total of 48 saliva samples from both male and female donors of multiple ethnicities, depositing the samples onto aluminium foil and drying overnight. Samples were then subjected to Raman analysis and the chemical signatures scrutinised to determine whether or not the saliva of male donors differed from that of female donors.

Raman Spectroscopy is a non-destructive analytical technique used for analyte identification based on molecular vibrations. As a basic explanation, monochromatic light is initially directed towards the sample, some of this light simply passing through the sample and some of it being scattered. A small amount of this scattered light experiences an energy shift due to interactions between the sample and the incident light. These energy shifts are detected and transformed into a visual representation. The resulting Raman spectrum typically plots frequency vs intensity of the energy shifted light. The positions of different bands on this spectrum relate to the molecular vibrations within the sample which, if interpreted correctly, can allow for the identification of analytes.

Raman spectra are somewhat characteristic of the chemical composition of the sample. In the case of the saliva analysed in this study, the features of the spectra were largely caused by amino acids and proteins. When comparing the respective spectra from male and female donors, by eye they appear remarkably similar. However using multivariate data analysis, a statistical technique used to analyse data with multiple variables, the researchers were able to distinguish between the saliva of male donors and that of female donors, reporting the ability to ascertain the sex of the donor with an accuracy of an impressive 94%.


Comparison of male and female saliva Raman spectra (Muro et al, 2016)

Although only a proof-of-concept paper, the research demonstrates the possibility of using portable Raman spectroscopy as a method of elucidating donor information, in this case sex, through the analysis of a bodily fluid. The researchers suggest further work will be conducted to include other bodily fluids and donor characteristics.

At this point, the usefulness of the research is limited. Although instantly establishing the sex of the donor of a bodily fluid can aid investigators in developing a suspect or victim profile more efficiently, the pool of potential donors is still huge. The total of 48 saliva donors used in this study is of course not a sufficient representation of the population, thus a much larger sample set would be required to fully evaluate the technique, including non-laboratory setting experiments. Furthermore, there is a wide range of medical conditions and additional factors that can result in changes in the chemical composition of saliva and thus could influence the effectiveness of this technique. Whether or not certain diseases or external influences can hinder gender determination using this method would need to be investigated.

Previous Research

The idea of utilising analytical chemistry to ascertain donor information is not in itself novel, and other researchers have attempted to achieve the same goal through different means.

In 2015, scientists also based at the University of Albany (Huynh et al, 2015) developed a biocatalytic assay approach to the analysis of amino acids in fingerprints to determine the sex of the donor. The study boasted an accuracy of 99%, with the sex differences believed to be due to the higher concentration of amino acids in fingerprints deposited by females.

Research by Takeda et al in 2009 used Nuclear Magnetic Resonance (NMR) Spectroscopy to determine differences between the urine and saliva samples of different donors based on the detection and comparison of different metabolites. Certain compounds, including acetate, formate, glycine and pyruvate, were found in higher concentrations in male samples, allowing for the differentiation between male and female bodily fluids.

The focus of such research is not limited to sex differentiation, for instance some research has even focused on establishing whether a blood sample belongs to a smoker or non-smoker. Utilising gas chromatography mass spectrometry with a solid phase microextraction pre-concentration step, Mochalski et al (2013) were able to effectively distinguish between the blood and breath of smokers and non-smokers due to the ten-fold increase in levels of benzene and toluene, a conclusion which has been repeated by other researchers.

Looking at just this small handful of studies, it becomes evident that certain analytical techniques have the potential power to ascertain a range of information about the donor of a bodily fluid. However all of these immunoassay and mass spectrometry techniques are typically time-consuming, requiring the transportation of a sample to a laboratory, sometimes extensive sample preparation, followed by a form of analysis that will often destroy the sample. This is evidentially not ideal during a time-sensitive criminal investigation in which sample amount may be limited.

To an extent, the research utilising Raman spectroscopy to determine sex from saliva does alleviate some of these problems. The portability of Raman devices allows for in situ analysis, removing the need for expensive and time-consuming laboratory analysis. As Raman spectroscopy is based on the interaction between the sample analyte and light, it is a non-destructive technique, allowing the sample to be preserved for storage and further analyses is required.

Although these techniques do not hold the power of DNA in almost irrefutably identifying the suspect, they may at least aid investigators in narrowing down their pool of suspects and steering the investigation in the right direction. No doubt further advances in analytical chemistry will allow for more accurate and robust techniques in the future.



Huynh, C et al. Forensic identification of gender from fingerprints. Anal. Chem. 87(2015), pp11531-11536.

Mochalski, P et al. Blood and breath levels of selected volatile organic compounds in healthy volunteers. Analyst. 7(2013), pp2134-2145.

Muro, C. L et al. Sex determination based on Raman Spectroscopy of saliva traces for forensic purposes. Anal. Chem. 88(2016), pp12489-12493.

Takeda, I et al. Understanding the human salivary metabolome. NMR Biomed. 22(2009), pp577-584.


Fragrance Forensics: Using Perfume to Catch the Culprit

Fragrance Forensics: Using Perfume to Catch the Culprit


Every day we apply chemicals to our bodies in the form of perfumes, colognes, deodorants and moisturisers, producing a concoction of pleasant scents that can be quite unique. It is well-known that perfumes and other fragrances can be potent and persistent, lingering on clothes and skin for hours if not days. Furthermore, these aromatic mixtures lend themselves to being easily transferred from one person to another through physical contact.

As the field of forensic science advances, investigators are looking for different ways in which they can identify suspects and connect individuals, and perfume may be an ideal target. What if the fragrance worn by an individual could be identified on a chemical level and used to link that person to a particular person or place? Simona Gherghel and fellow researchers at University College London have aimed to achieve this using analytical chemistry techniques.


Linalool (left) and limonene (right), common components in perfumes and colognes.

Different perfumes and colognes are composed of a variety of volatile organic compounds (VOCs), which provide the products with their powerful and characteristic scents. Compounds commonly detected in such products include linalool, limonene, coumarin, geraniol and eugenol, often in varying quantities and mixed with an assortment of other components. Once applied, these fragrances are absorbed by clothing and skin and can be readily transferred to fabrics and other surfaces.

Using gas chromatography-mass spectrometry (GC-MS), a well-established analytical technique frequently utilised in forensic enquiries, the team analysed fragrances in a number of scenarios to investigate the extent to which chemical components could be transferred between surfaces and what circumstances might affect this transfer.

The research focused on a number of factors relevant to the use of fragrances as a potential form of trace evidence in forensic enquiries, specifically the method of transfer and the time between application of the fragrance and contact with another surface. Experiments involved contact between swatches of fragranced and fragrance-free fabrics, examining transfer of compounds when the fabrics were in contact with no friction, and forcefully rubbed together over periods of time ranging from 1 minute to 60 minutes. After controlled contact, swabs were collected from the fabrics and subjected to GC-MS analysis. Unsurprisingly, extended contact time led to an increase in transferred components. This may have the potential to indicate how long a victim and offender were in physical contact, whether it be fleetingly or for a prolonged period of time, the latter being more likely in the case of an assault.

This research also investigated the effects of time passed between application of a fragrance product and contact between two surfaces on the transfer and persistence of VOCs. Contact between a fragranced piece of fabric and a fragrance-free swatch was investigated at a number of time points ranging from contact occurring 5 minutes after fragrance use and to 7 days after use. As was expected, the number of chemical compounds transferred between the fabric swatches decreased with time, with larger-sized, less volatile molecules persisting for longer. When only 5 minutes had passed before contact occurred, an average of 24 volatile components were transferred from the perfumed fabric. However after 6 hours only 12 components were detected, and this decreased to only 6 components after 7 days. Although this shows that certain transferred chemical compounds can persist for days, there is a discernible decrease in their presence which ultimately makes the sample less detectable and less unique, as a smaller mixture of chemicals are available for identification and comparison.

Although this is the first published work demonstrating the transfer of fragrance between garments in a forensic setting, the possibility of identifying perfumes based on their chemical composition for forensic purposes has been previously examined by experts at Staffordshire University in the UK. Led by PhD student Alison Davidson, the team has been compiling chemical profiles of popular perfumes and colognes with the hope of distinguishing between brands of difference fragrances and ultimately using this information to aid criminal investigations.

The ability to identify perfumes and establish physical contact between two individuals based on VOCs could be of particular use in the investigation of sexual assaults and other violent crimes in which the victim and offender were in close contact. For instance, the contact between a victim’s perfumed clothing and the clothing of the offender could cause the transfer of volatile organic compounds to the offender’s clothing (or vice versa). Later analysis of a suspect’s clothing may then result in the identification of chemical compounds originating from the victim’s perfume, indicating physical contact and thus potentially supporting an accusation.

Although the research conducted has supported the possibility of utilising transferred VOCs in perfume and possible affecting factors to aid legal investigations, it is vital to consider that a greater range of variables must be taken into account if such analyses were to be utilised in real life scenarios. The degree of activity by the victim and offender and the time passed between the offense and forensic analysis must be considered, as should how unique the mixture of chemical components detected really is. Furthermore, if the transfer of perfume between fabrics can occur so easily, there is a distinct possibility that such a transfer could occur in entirely innocent circumstances, highlighting the importance of such analysis only being utilised alongside alternative sources of evidence.

The concept of studying the chemical composition of perfumes and fragrances to aid legal investigations is very much in its infancy, but with further research this technique may have the potential to offer investigators an additional tool to sniff out suspects.



S. Gherghel, et al., Analysis of transferred fragrance and its forensic implications, Sci. Justice (2016), 10.1016/j.scijus.2016.08.004


Killer Cocktails: The Chemistry Behind the Lethal Injection

Killer Cocktails: The Chemistry Behind the Lethal Injection

In many countries worldwide, including the United States, lethal injection is used as a humane method of executing a death row inmate. With the lethal injection, the life of the inmate can theoretically be cleanly and swiftly ended through administering a number of drugs, with no pain and minimal trauma.

The debate over the lethal injection hit the news again last month when the U.S. Supreme Court ruled against claims that the use of a drug used in lethal injections (midazolam hydrochloride) violates the Eighth Amendment (relating to prohibiting cruel and unusual punishment). Despite this method of capital punishment largely replacing supposedly less humane forms of death such as the electric chair and hanging, there is still great debate over the ethics of certain drugs used, and whether they actually do provide a swift and pain-free death.

But what drugs are involved in this lethal cocktail, and how do these end life in an apparently ethical manner?

The procedure for lethal injection can vary across different countries and even different states. In the United States, execution by lethal injection is typically achieved through the intravenous use of three drugs in succession, each with a different purpose, though in some instances a single-drug method is used, usually involving a lethal dose of anaesthetic.

Sodium Thiopental (Source: Chemspider)

Sodium Thiopental (Source: Chemspider)

But let’s look at the three-part cocktail. The first drug to be administered is usually a barbiturate to act as an anaesthetic (painkiller), used to ensure the remaining steps in the procedure do not cause any pain. Traditionally sodium thiopental is used, a fast-onset but short-acting barbiturate. Barbiturates are compounds which can ultimately produce anaesthetic effects. They act as agonists of gamma-aminobutyric acid (GABA) receptors, which are inhibitory neurotransmitters in the central nervous system. By binding to this receptor, the activity of the central nervous system is depressed, bringing about effects ranging from mild sedation to general anaesthesia. In this instance, a sufficient dosage is administered to render the inmate unconscious, thus ensuring a painless procedure. However some have argued that the fast-acting effects of sodium thiopental can wear off before the execution procedure is complete.

Succinylcholine Chloride (Source: Chemspider)

Succinylcholine Chloride (Source: Chemspider)

Once the inmate is unconscious, a neuromuscular-blocking drug is then administered, generally succinylcholine (also known as suxamethonium chloride) or pancuronium bromide. Compounds such as succinylcholine bind to acetylcholine receptors, blocking the action of acetylcholine, a neurotransmitter essential in the proper functioning of skeletal muscle. When succinylcholine binds to this receptor, a cation channel in the receptor opens and depolarisation of the neuromuscular junction occurs. Normally when acetylcholine binds to this receptor, it soon dissociates following depolarisation and the muscle cell will be ready for the next signal. However compounds such as succinylcholine have a significantly longer duration, ultimately resulting in paralysis. In short, administering a drug such as succinylcholine prevents acetylcholine from communicating with the muscles and thus paralyses the inmate’s muscles, including those used to breathe. Other drugs such as pancuronium bromide can also be used, which have a different mechanism of action but ultimately achieve the same final result of muscle paralysis.

Finally the salt potassium chloride is administered. Within the body a variety of salts are vital for brain function, transmission of nerve signals and the beating of the heart, and these salt levels are tightly regulated by the body. In the normal functioning of the body, the majority of potassium is confined to the cells, with very little being present in the bloodstream at any one time. The introduction of a large amount of potassium chloride disrupts this electrochemical balance as the body’s cell are not able to equilibrate, rendering the cells unable to function, leading to cardiac arrest. In simpler terms, the overdose of potassium chloride brings about a condition known as hyperkalemia, in which the potassium concentration in the body is too high, causing the heart to fail. The inmate is officially declared dead when a cardiac monitor indicates the heart has stopped.

Recently, the drug used to initially render the inmate unconscious, sodium thiopental, has been difficult to obtain for a number of reasons, thus some states in the U.S. have used midazolam hydrochloride, a drug which has ultimately caused a great deal of controversy in recent years, such as in the Clayton Lockett case. This benzodiazepine is commonly used as a sedative, but when used during the lethal injection procedure, it is generally combined with an opiate. This is because midazolam itself has no analgesic (painkilling) effect, thus an additional drug is required to achieve this. Despite its recent use, claims have been made that a number of executions using this drug resulted in the prisoners showing signs of consciousness and gasping, suggesting that they were not quite as unconscious as intended. If the inmate is not unconscious when the muscle paralyser and electrolytes are administered, they may experience suffocation due to the muscle paralysing agent and burning caused by the potassium chloride.

So there we have it – some of the primary drugs administered during the lethal injection procedure and how they react within the body to bring about death. For more information on the death penalty (namely in the U.S), visit the Death Penalty Information Center.


Johnson, B. A. 2011. Addiction Medicine: Science and Practice Volume 1. New York: Springer.

Kroll, D. 2014. The Drugs Used in Execution by Lethal Injection. [online] Available from:

Kemsley, J. 2015. Sedative for Lethal Injections Affirmed. [online] Available from:

Cover Image Credit: Thomas Boyd (The Oregonian)