Helping authorities detect fentanyl analogues

The past several years has seen growing awareness of a drug called fentanyl, which is increasingly cited in relation to drug overdoses, including many high profile deaths, as well as becoming the focus of many law enforcement agencies, especially in the United States.

macro of pills

The U.S. Drug Enforcement Administration (DEA) have named fentanyl the most significant synthetic opioid threat in the U.S. in 2018, while the Centre for Disease Control in the United States have determined that the rate of drug overdose death from synthetic opioids, not including methadone, doubled in just one year from 2015 to 2016. In 2016, opioids caused 42,000 deaths, and nearly half of those were fentanyl-related, including the deaths of Prince, Tom Petty and Lil Peep.

But is fentanyl a new drug? And if not, why has it suddenly become a major factor in the opioid crisis?

Fentanyl was first synthesised in 1959 by Paul Janssen and has been used as a pain reliever and general anaesthetic in operating rooms. While there are legitimate uses for fentanyl, it presents a formidable public health risk, especially in the United States. While some drug users seek it out for recreational use, many are unaware that what they are buying is fentanyl, as illicit drug makers use it to adulterate more expensive pharmaceuticals and opioids, like heroin. It is 80 to 100 times more potent than morphine, and while it only costs $6,000 to purchase one kilogram of fentanyl in a lab, that one kilogram can have a distribution value of up to $1.6 million. This presents an enormous economic motive for replacing common opioids with fentanyl.

Fentanyl analogues, or compounds with a similar molecular structure, make it even more difficult to regulate. Analogues are manufactured in labs, and once one is discovered by law enforcement and outlawed, another analogue is already waiting to be put into use. Some, like carfentanil, are particularly dangerous. Carfentanil is 100 times stronger than fentanyl (making it 10,000 times stronger than a unit of morphine), and as such, is used to sedate large mammals, like elephants. These highly potent drugs can rapidly incapacitate by causing central nervous and respiratory depression.

Our Sport and Specialised Analytical Services team performs analysis for forensics laboratories, including those working with police authorities and coroners, to detect and identify drugs in body fluids and drug seizures.  Work is also performed to understand more about how the latest drugs are metabolised in the body. The study of drug metabolism, or pharmacokinetics, is vital to understanding how drugs break down in the human body.  In a forensic environment it is very important to know how the body changes a drug in order to be able to detect it in forensic tests.

Scientists at LGC Simon Hudson and Charlotte Cutler studied the metabolic fate of several analogues of fentanyl, including carfentanil, and published three white papers on their findings. Each paper goes through their methodology, which can be used as an aid to detect the analogues in biological fluids.

In one of the case studies, Simon studied carfentanil in post mortem blood samples.  Not much has been understood about the metabolism of carfentanil, which suggests that the true extent of carfentanil-related deaths is unknown. After analysing over 70 carfentanil cases, Simon found that the parent drug was always present in blood and urine post mortem and that in some cases, due to the low levels of carfentanil, extremely sensitive analytical equipment was required detect it’s presence.

In the other papers, Simon and Charlotte studied samples from UK siezures of drugs that were originally reported by authorities in Latvia and Slovenia between December 2016 and August 2017. They were able to identify many metabolites of cyclopropylfentanyl and methoxyacetylfentanyl. These studies are a beneficial tool to help authorities and scientists detect these analogues in the future.

To learn more about the history of fentanyl, its chemistry and current issues, watch our interesting webinar. And to understand more about Simon’s work and studies on the drug, read the white papers on carfentanil, methoxyacetylfentanyl, and cyclopropylfentanyl.

Alzheimer’s disease diagnosis: the end of the guessing game?

There are currently around 850,000 people living with dementia in the UK, and the number of people affected is expected to reach 2 million by 2051. The costs associated with dementia, estimated now at £26 billion a year, are likely to treble.

Alzheimer’s disease is the most common type of dementia, affecting between 60 and 80 percent of those diagnosed. There is no known cure, with treatments limited to preserving cognitive function. Currently, there is no non-invasive method for diagnosing Alzheimer’s disease with GP’s relying on in depth cognitive tests, with clinical confidence in diagnosis typically at 70-80%.

Doctor Helping Elderly

If confident early diagnosis could be achieved through noninvasive techniques, treatment could be introduced earlier delaying the onset of memory impairment.

The solution

The development of plaques or tangles of certain proteins (β-amyloid and tau proteins) in the brain is a known feature in Alzheimer’s disease. It is also known that abnormal accumulation of metals underlies several neurodegenerative diseases. Iron, in particular, is associated with the formation of neurofibrillary tangles in the β-amyloid plaques. The recent advances in the use of Magnetic Resonance Imaging (MRI) for the earlier detection of neurological diseases require validation to ensure the integrity of the images obtained is adequate for diagnostic purposes.

Researchers at LGC, in collaboration with partners, have been working to establish a link between novel MRI scans and quantitative elemental mapping of soft tissues. A method of mapping the levels of iron in sections of the brain using laser ablation (LA) coupled to Inductively Coupled Plasma Mass Spectrometry (ICP-MS) has been developed, along with a novel calibration strategy and standard to support quantitative tissue imaging. Correlation of the metal content associated with β-amyloid protein and MRI images will help diagnosis of AD at an early stage, where preventative therapy will have greater impact.

LGC has developed a novel calibration strategy for LA-ICP-MS that produced quantitative images for iron in whole mouse brain sections (provided through collaboration with Kings College London and the University of Warwick) and compared them with results from micro x-ray fluorescence (μ-XRF) (provided through collaboration with Ghent University and the University of Warwick). The data showed good agreement in total iron concentrations for a selection of areas within the mouse brain sections. This finding supports the proposed method as a quantitative approach; the calibration strategy has been published in the Journal of Analytical Atomic Spectrometry¹.

Impact

The development of this method for quantitative imaging of iron in the brain has the potential to lead to techniques for earlier diagnosis of Alzheimer’s disease, enabling earlier intervention, therapies and treatment aimed at delaying the onset of symptoms.

Delaying the onset of neurodegenerative disorders, such as Alzheimer’s disease, by five years could halve the number of deaths from the condition, saving 30,000 lives a year and billions of pounds in treatment costs. Reducing severe cognitive impairment in the elderly by 1% pa would cancel all estimated increases in long-term care costs due to our ageing population.

The methodology will also provide deeper understanding of the early development of Alzheimer’s disease leading the way for new treatments aimed at preventing the disease.

Heidi Goenaga-Infante, Principal Scientist for inorganic analysis at LGC, commented: “This cutting-edge research is already proving to be of significant benefit to the validation of non-invasive diagnostic tools for Alzheimer’s disease. The potential for metal imaging mass spectrometry of other biological tissues to probe the reported links between metals and disease states is now a step closer.”

If you’d like to learn more about our work and read other case studies, visit our website.

¹ J O’Reilly, D Douglas, J Braybrook, P.-W. So, E Vergucht, J Garrevoet, B Vekemans, L Vinczec and H Goenaga-Infante, “A novel calibration strategy for the quantitative imaging of iron in biological tissues by LA-ICP-MS using matrix-matched standards and internal standardisation”, J Anal. At. Spectrom., 2014, 29, 1378-1384