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Researchers have taken major steps in drug analysis. While medication is often prescribed as a way to relieve the stresses and traumas following combat, more than 20 percent of military people with post-traumatic stress disorder have developed a drug or alcohol addiction. Although there are treatments for substance dependence, including medication to reduce its use (Buprenorphine), tests performed by Veterans Affairs hospital physicians that check for recurring drug use usually involve collecting urine samples and sending to a lab for analysis, which could take up to two weeks. But now you don’t have to wait that long. In fact, you could get test results while the individual is still in the VA hospital so that treatment can be quickly adjusted. Real-Time Analyzers Inc. has been developing a surface-enhanced Raman spectroscopy (SERS)-based assay that can detect and identify numerous drugs in saliva at ng/mL concentrations within 10 minutes. The sample collection from subjects began in August 2015 and is ongoing. While the first field-usable Raman spectrometer was developed more than a decade ago, today the company uses a hand-held version to measure the drugs in saliva. The Connecticut-based company that designs and manufactures Raman analyzers for use in field, plant and laboratory settings partnered with CT Veterans Affairs Hospital, so all of its subjects were in fact military personnel. “The goal is to try and help our veterans reduce their addiction to the drugs that they started taking when they were in the field,” Stuart Farquharson, Ph.D., Board of Directors member & president at Real-Time Analyzers told R&D Magazine after his session at Pittcon in Atlanta earlier this month, titled Clinical Toxicology: Analysis of Drugs in Saliva During Treatment of PTSD Patients. “To do that, we need to monitor that they’re taking the drugs that are trying to help them and that’s been the biggest issue, we need a point-of-care measurement so you know what the situation is when the doctor is talking to them each time they visit.” Co-authors of this study also included Katie Dana, Chetan Shende and Dr. Albert Arias. According to the Substance Abuse and Mental Health Services Administration, 23.9 million Americans currently use illicit drugs, and 6.8 million Americans misuse prescription drugs. The most common drugs prescribed to PTSD patients are Benzodiazepines and an addictive anxiety medication called Diazepam. As a result, the SERS analyzer was developed to provide the following: Real-Time Analyzers used the portable drug analyzer by collecting 1 mL of saliva, added a sample of reagent tube, passed the sample through a filter into Lab-on-chip, then inserted the LOC into the portable Raman analyzer. The device extracted drugs using SLE. The team measured 150 drugs, looking for the standard ones of abuse, such as cocaine and prescription drugs. The researchers also developed a spectral search and match software to ID the drugs found in the subject’s saliva. “In the end we were able to get a measurement that was pretty consistent,” Farquharson said during the session. The research team’s findings were “shocking,” according to Farquharson—of the more than 100 samples measured, very few of them had any drugs at all in their system, save for “street drugs.” “That’s another part of the scenario—they (veterans) are selling the medication they’re using to get other drugs, which is really unfortunate,” he added. While the research team achieved the required 10-50 nanograms/mL sensitivity for many of the drugs in water samples, they still need to improve the extraction method to obtain the same sensitivity in saliva samples. “Our goal is to have an analyzer and method that can identify and quantify drugs in saliva within 10 minutes of sample collection. This would provide doctors with the ability to evaluate PTSD patients during office visits. The analyzer would also allow rapid identification of drug type in emergency-room overdose patients,” Farquharson concluded. Establish your company as a technology leader! For more than 50 years, the R&D 100 Awards have showcased new products of technological significance. You can join this exclusive community! Learn more.

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Site: www.sciencenews.org

For some people, fentanyl can be a life-saver, easing profound pain. But outside of a doctor’s office, the powerful opioid drug is also a covert killer. In the last several years, clandestine drugmakers have begun experimenting with this ingredient, baking it into drugs sold on the streets, most notably heroin. Fentanyl and closely related compounds have “literally invaded the entire heroin supply,” says medical toxicologist Lewis Nelson of New York University Langone Medical Center. Fentanyl is showing up in other drugs, too. In San Francisco’s Bay Area in March, high doses of fentanyl were laced into counterfeit versions of the pain pill Norco. In January, fentanyl was found in illegal pills sold as oxycodone in New Jersey. And in late 2015, fentanyl turned up in fake Xanax pills in California. This ubiquitous recipe-tinkering makes it impossible for users to know whether they’re about to take drugs mixed with fentanyl. And that uncertainty has proved deadly. Fentanyl-related deaths are rising sharply in multiple areas. National numbers are hard to come by, but in many regions around the United States, fentanyl-related fatalities have soared in recent years. Maryland is one of the hardest-hit states. From 2007 to 2012, the number of fentanyl-related deaths hovered around 30 per year. By 2015, that number had grown to 340. A similar rise is obvious in Connecticut, where in 2012, there were 14 fentanyl-related deaths. In 2015, that number was 188. In Massachusetts, two-thirds of people who died from opioid overdoses in the first half of 2016 showed signs of fentanyl. This wave of fentanyl-related overdoses is “horrendous,” says Daniel Ciccarone of the University of California, San Francisco. What’s worse, he says, “I think it’s here to stay.” Fentanyl is not a new drug. Available in the 1960s, it is still used in hospitals as an anesthetic and is available by prescription to fight powerful pain. What’s new, Ciccarone says, is that clandestine drug manufacturers have discovered that the euphoria-producing opioid can be made cheaply and easily — no poppy fields necessary. Fentanyl is about 30 to 40 times stronger than heroin and up to 100 times more powerful than morphine, which means that a given effect on the body can be achieved with a much smaller amount of fentanyl. Inadvertently taking a bit of fentanyl can cause big trouble. “It’s a dosing problem,” Nelson says. “Because the drug is so potent, little changes in measurements can have very big implications for toxicity. That’s really the problem.” That problem is made worse by the variability of illegal drugs — users often don’t know what they’re buying. Illegal labs aren’t pumping out products with carefully calibrated doses or uniform chemical makeup. The drugs change from day to day, making it nearly impossible for a user to know what he or she is about to take, Ciccarone says. He has seen this struggle up close. Drug users have told him that the products they buy are unpredictable. Another thing people are telling him: “That they and their friends and compatriots are dropping like flies.” Tellingly, some of the most experienced drug users have recently begun doing “tester shots,” small doses to get a sense of the type and dose of drug they’re about to use, Ciccarone says. Users are right to be wary. Typically, opioids can kill by gradually depressing a person’s ability to breathe. Illicit fentanyl, a recent study suggests, can kill within minutes by paralyzing muscles. Doctors have known that when injected quickly, fentanyl can paralyze chest wall muscles, prevent breathing and kill a person rapidly. That effect, called “wooden chest,” might help explain the rise in fentanyl-related deaths, scientists report in the June Clinical Toxicology. A quick injection of fentanyl “literally freezes the muscles and you can’t move the chest,” says toxicologist Henry Spiller of the Central Ohio Poison Center in Columbus. That’s why doctors who dispense fentanyl in the hospital intentionally proceed very slowly and keep the opioid-counteracting drug naloxone (Narcan) on hand. “If you give it too fast, we know this occurs,” Spiller says. But it wasn’t known whether this same phenomenon might help explain the death rate of people using the drug illegally. Spiller and colleagues tested post-mortem concentrations of fentanyl and its breakdown product norfentanyl in 48 fentanyl-related deaths. The body usually begins breaking down fentanyl into norfentanyl within two minutes, an earlier study found. Yet in 20 of the cases, the researchers found no signs of norfentanyl, indicating death came almost immediately after first receiving fentanyl. Naloxone can counteract the effects of opioids if someone nearby can administer the antidote. But for people whose chests quickly freeze from fentanyl, resuscitation becomes more unlikely. Fentanyl “is just a bad drug,” Spiller says. Fentanyl’s danger is magnified for people not accustomed to taking opioids, such as those addicted to cocaine, a situation illustrated by a recent tragedy in New Haven, Conn. New Haven authorities noticed a string of suspicious overdoses in late June, leaving three people dead. Drug users thought they were buying cocaine, but the drugs contained fentanyl, says analytical toxicologist Kara Lynch of the University of California, San Francisco. As one of the handful of labs capable of testing blood and urine for fentanyl, hers was called on to identify the culprit. Her lab spotted fentanyl in Norco tablets back in March. Lynch’s group uses high-resolution mass spectrometry to detect many drugs’ chemical signatures. But this method reveals only the drugs scientists suspect. “We can look for what we know to look for,” she says. And success depends on getting the samples in the first place. The logistical hurdles of figuring out exactly what a person took, and how much, and when, are large. Ciccarone contrasts the situation with cases of food poisoning. When people start getting sick, public health officials can figure out what lettuce people ate and test it for pathogens. The same kind of tracking system doesn’t exist for drugs. His efforts to develop a system for testing illegal drugs in Baltimore broke down in part because no one had time to do the work. “The coroner is so busy right now with dead bodies,” he says. “They don’t have the time to test the ‘lettuce.’ ” In the quest to curb fentanyl-related deaths, scientists and public health officials are searching for new strategies. Spiller advocates a more targeted public health message to users, one that emphasizes that fentanyl is simply a deadly drug, not just a more potent high. Ciccarone says that facilities where drug users can take illegal drugs under the care of medical personnel might reduce the number of fatalities. For now, the scope of the problem continues to grow, Nelson says. The situation is made worse by the ingenuity of illicit drugmakers, who readily experiment with new compounds. Fentanyl itself can be tweaked to create at least 16 related forms, one of which, acetyl fentanyl, has been linked to overdose deaths. New drugs and new tweaks to old drugs rapidly evolve (SN: 5/16/15, p. 22), Nelson says, creating a game of whack-a-mole in which designer drugs confound public health officials and law enforcement. “There is no single easy solution to this problem,” he says.

Dargan P.I.,Clinical Toxicology | Dargan P.I.,Kings College London | Albert S.,Foundation Medicine | Wood D.M.,Clinical Toxicology
QJM | Year: 2010

Background: Mephedrone is a synthetic cathinone that is commonly used as a recreational drug among those who attend nightclubs. There have been increasing reports of toxicity associated with its use and it was controlled as a Class B drug under the Misuse of Drugs Act (1971) in the UK on 16 April 2010. There has been a suggestion from media reports that mephedrone use is common in children/students but there is no data on the prevalence of its use among the general population. The aim of this study was to determine the prevalence and frequency of use of mephedrone among school and college/university aged individuals and to collect data on the sources of mephedrone and acute harm related to its use.Methods: Data was collected using a questionnaire survey in schools, colleges and universities in the Tayside area of Scotland, UK in February 2010.Results: A total of 1006 individuals completed the survey [501 (49.8%) males and 505 (50.2%) females], of whom 349 classified their educational institute as a school and 657 as a college/university. Among them 205 (20.3%) reported previous use of mephedrone; 23.4% reported using only using mephedrone on one occasion previously, although 4.4% reported daily use. A total of 56% of those who had used mephedrone, reported at least one unwanted effect associated with its use. A total of 17.6% of users reported 'addiction or dependence' symptoms associated with their mephedrone use. A total of 48.8% of users sourced mephedrone from street level dealers, 10.7% from the Internet.Conclusions: We have shown in this study that the use of mephedrone among school and college/university students is common and that users found it easy to obtain. There was a high prevalence of unwanted effects associated with its use. Further work is needed to determine the impact of the recent changes in the UK legislation relating to mephedrone and other related cathinones and whether this has been effective in reducing the prevalence of mephedrone use. © The Author 2010. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved.

Wood D.M.,Clinical Toxicology | Wood D.M.,Kings College London | Davies S.,St Georges, University of London | Puchnarewicz M.,St Georges, University of London | And 3 more authors.
European Journal of Clinical Pharmacology | Year: 2012

Purpose: Long-term regular use of ketamine has been reported to be associated with severe symptomatic urinary tract problems. Methoxetamine, an arylcyclohexylamine derivative of ketamine, is marketed as a "bladder safe" derivative of ketamine, and no cases of acute toxicity following analytically confirmed methoxetamine use have been reported to date. We report here a case series of three individuals with acute toxicity related to the analytically confirmed use of methoxetamine. Case series Three patients aged between 28 and 42 years presented to the Emergency Department (ED) on unrelated occasions having used methoxetamine. Clinical features were suggestive of a "dissociative/catatonic" state similar to that seen with ketamine; in addition, they had clinical features of acute sympathomimetic toxicity with significant tachycardia and hypertension. All were managed with low-dose benzodiazepines and discharged home once their symptoms/signs had settled. Toxicological screening Serum collected at the time of presentation to the ED was analysed qualitatively and quantitatively by gas chromatography-mass spectrometry. Serum concentrations ranged from 0.09 to 0.2 mg/L; in addition, detectable levels of 6-APB/5-APB were found in one of the patients. Conclusions: These three analytically confirmed cases demonstrate that acute methoxetamine-related toxicity is associated with both "dissociative" and "sympathomimetic" clinical features. The information from these three cases is useful to clinical pharmacologists, not only in managing individuals with acute methoxetamine toxicity but also in advising the appropriate legislative authorities on the risk of acute harm related to methoxetamine use. Further work is needed to determine whether methoxetamine is more "bladder friendly" than ketamine, as has been suggested by those marketing methoxetamine. © Springer-Verlag 2011.

Wood D.M.,Clinical Toxicology | Wood D.M.,Kings College London | Dargan P.I.,Clinical Toxicology | Dargan P.I.,Kings College London
Substance Use and Misuse | Year: 2014

Alpha-methyltryptamine (AMT) is a novel psychoactive substance available over the Internet. This study used European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) Internet snapshot methodology to investigate the availability and cost of AMT in March/October 2012. From March to October 2012, there was a decrease in the number of Internet sites selling AMT (44 to 31). AMT powder was cheaper in "bulk" (100 g) than in "recreational- user" (100 mg) quantities, and there was a decrease in price. Data from Internet snapshot surveys complement and allow triangulation of data from other sources to build a more detailed picture on availability and use of novel psychoactive substances. Copyright © 2014 Informa Healthcare USA, Inc.

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