Driving Impairment Cases Involving Flualprazolam.

Flualprazolam is a novel psychoactive substance in the benzodiazepine class that is increasing in prevalence in the USA. This study describes 19 cases of drivers stopped for impaired driving where flualprazolam was detected. This represents ∼9% of the total cases submitted to the Sedgwick County Regional Forensic Science Center toxicology laboratory between July 2019 and May 2020. Blood concentrations of flualprazolam ranged from 4 to 69 ng/mL, with mean and median concentrations of 20.9 ng/mL and 15 ng/mL, respectively. The increased prevalence in which laboratories are detecting flualprazolam along with the low concentrations necessary for pharmacological effects illustrates the importance of laboratories to remain vigilant in testing for novel psychoactive substances.

1,1-Difluoroethane Forensic Aspects for the Toxicologist and Pathologist.

1,1-Difluoroethane (DFE) is a halogenated hydrocarbon that is commonly used as a propellant in air duster products. Herein, the pharmacology of DFE was reviewed, and questions relevant to medicolegal investigations were addressed. Particular emphasis was given to detection time in biological specimens and the range, onset and duration of effects. DFE may be abused as an inhalant and is rapidly absorbed through the lungs. Onset of central nervous system (CNS) depressant effects is within seconds and the duration may only last minutes. The effects may lead to impairment of human performance, including confusion, lethargy, impaired judgment, loss of motor coordination and loss of consciousness. Death may result even after the first use. With heavy use or in combination with other CNS depressants, extended periods of drowsiness or loss of consciousness may be observed with an increased risk of a fatal event. A majority of impaired driving investigations where DFE was identified included a collision demonstrating the significant impact its use may have on traffic safety. When DFE is identified alone, without other drugs that cause CNS impairment, the effects may not be observable minutes after the crash, making identification of its use difficult. Although concentrations dissipate rapidly, DFE has been detected in blood specimens collected up to 3 hours after the driving incident. Two studies on passive exposure presented herein demonstrated that it is unlikely to detect DFE above concentrations of ∼2.6 µg/mL in blood or urine due to even extreme unintentional exposure. Alternative specimens such as brain, lung and tracheal air should be considered in some postmortem investigations. DFE has been identified in blood specimens from postmortem cases at concentrations from 0.14 to 460 µg/mL and in impaired driving cases from 0.16 to 140 µg/mL.

Driving Impairment Cases Involving Etizolam and Flubromazolam.

This study describes 12 cases of drivers stopped for impaired driving, where a designer benzodiazepine was detected, specifically etizolam or flubromazolam. Etizolam was detected in three cases, with blood concentrations ranging from 40 to 330 ng/mL. Two of these cases had low concentrations of methamphetamine and/or amphetamine, and in the third case tetrahydrocannabinol (THC) was detected. Flubromazolam was detected in nine cases; in all cases, at least one other drug was detected, with THC being the most prevalent. The mean blood concentration of flubromazolam was 16.3 ng/mL and had a median concentration of 17.0 ng/mL, ranging from 7.0 to 31 ng/mL. The low concentrations of designer benzodiazepines that produce pharmacological effects may allow many of these drugs to go undetected using routine testing in laboratories; therefore, it is necessary to include these novel compounds within validated analytical methods to reduce the chance of reporting false negative results. The prevalence in which laboratories are detecting the presence of novel benzodiazepines in impaired drivers illustrates the increased threat to public safety. These case studies demonstrate the importance of investigating agencies and forensic laboratories to be vigilant in monitoring the emerging novel psychoactive substances in their region.

Fentanyl and Driving Impairment.

The incidence of fentanyl in forensic toxicology analyses in the USA has dramatically increased over the past several years. The increase in death cases has been well studied; however, little has been reported on the impact to drug impaired driving. Fentanyl driving while under the influence of drugs (DUID) case data from 2014 to 2019 is presented. The data were obtained from three toxicology laboratories in the Northeast, Southeast, and Midwest regions of the USA. Fentanyl whole blood concentrations ranged from 0.1 to 157 ng/mL in living drivers with a 466% to 524% increase in fentanyl-positive DUID cases from 2014 to 2019, depending on the US region. The vast majority of fentanyl cases involved poly-drug use. Twenty case histories are presented where fentanyl was the only drug identified. The mean (standard deviation) fentanyl concentration for these cases was 5.2 ± 3.8 ng/mL with a median of 3.7 ng/mL, and the concentrations ranged from 2.0 to 16 ng/mL. Naloxone administration was documented in exactly half of these cases similar to another study involving carfentanil-impaired driving. The case histories also demonstrate that some recreational opioid users may display limited signs of impairment either due to tolerance or naloxone administration. The top three observations in common among the cases were the driver was found unresponsive behind the wheel, the vehicle left the travel lane or roadway, and the driver was involved in a crash. The increase in fentanyl use not only poses a risk for overdose and death, but is also a significant concern for traffic safety. This study supports the movement of fentanyl from a Tier II drug to Tier I due to its significant potential for impairment and increase in prevalence in impaired driving cases.

Roadside drug testing: An evaluation of the Alere DDS® 2 mobile test system.

The number of drivers using drugs has increased over the last few years, and is likely to continue its upward trend. Testing drivers for alcohol use is routine and standardized, but the same is not true for the identification of driving under the influence of drugs (DUID). The Drug Evaluation and Classification Program (DECP) was developed to train police officers to recognize the signs and symptoms of recent drug use and remains an invaluable program; however, there are insufficient numbers of these highly trained drug recognition experts (DREs) available to attend every potential drug involved traffic incident. While blood and urine samples are used to test for drugs in a driver, both have disadvantages, particularly as they pertain to the length of time required after a traffic stop to sample collection. Therefore, the development of oral fluid testing devices which can be operated at the roadside and have the potential to assist officers in the identification of drug use is a major advancement in DUID cases. This project evaluated the performance of one instrumental oral fluid roadside testing device (Alere DDS®2) compared to DRE opinion, oral fluid laboratory-based analysis, and routine blood testing. The results showed that there was a good correlation with DRE observations and the device performance was >80% in all drug categories compared to laboratory-based analytical testing, both in oral fluid and blood, with few exceptions. The instrument can be considered a useful tool to assist law enforcement in identifying a drugged driver. Because the device does not test for all potentially impairing drugs, the opinion of the police officer regarding the condition of the driver should still be considered the most important aspect for arrest and further action.

U-47700: A Not So New Opioid.

U-47700 was developed by the Upjohn Co. in the 1970s as part of their search for a selective µ-opioid agonist with similar potency as morphine. U-47700 has re-emerged recently in the illicit drug market and is easily and cheaply obtained via the internet as well as on the street, many times falsely sold as another drug. Several fatalities from U-47700 have been reported in scientific literature, often in combination with other intoxicants. This case report describes the first death in south-central Kansas resulting solely from U-47700 intoxication: a 26-year-old white male found dead in his bedroom with apparent drug paraphernalia. Autopsy findings were consistent with opioid overdose, but toxicological examination, utilizing immunoassay and instrumental techniques, was negative for opioids. U-47700 was detected in a comprehensive alkaloid screen by GC/MS and GC-NPD, and quantitation was performed using GC-NPD on a variety of specimens to provide a full tissue distribution. Quantitation of U-47700 in this individual revealed the following: heart blood 0.26 mg/L, femoral blood 0.40 mg/L, vitreous fluid 0.09 mg/L, brain 0.38 mg/kg, liver 0.28 mg/kg and urine 4.6 mg/L.

Brain tissue: a viable postmortem toxicological specimen.

Brain tissue may be a valuable specimen in interpretation of postmortem toxicology. The protected and isolated position of the brain eliminates or at least attenuates many of the interpretive challenges with postmortem blood specimens. This study presents data for 30 drug and drug metabolites in cases submitted to the Sedgwick County Regional Forensic Science Center for autopsy examination from 2007 to 2014. Drug concentration in heart and femoral blood is compared with the drug concentration in brain tissue. There is a positive correlation of blood to brain concentrations, thus providing another tool for the toxicologist or pathologist to utilize in case interpretation.

Identification and quantitation of ketamine in biological matrices using gas chromatography-mass spectrometry (GC-MS).

Ketamine hydrochloride, a Schedule III drug under the Controlled Substances Act, is a dissociative anesthetic that has a combination of stimulant, depressant, hallucinogenic, and analgesic properties. This procedure utilizes solid phase extraction of blood, tissue, or urine samples to isolate ketamine (special K) and its metabolite norketamine. The extract is then assayed using selected ion monitoring gas chromatography/mass spectrometry for absolute structural confirmation of the compound and the compounds quantified by comparing responses of the unknown samples to the responses of standards.

Identification and quantitation of zolpidem in biological matrices using gas chromatography-mass spectrometry (GC-MS).

Zolpidem is a short-acting nonbenzodiazepine hypnotic used for the treatment of insomnia. It works quickly and has a short half-life of 2-3 h. Significant side effects are reported including dizziness, amnesia, and even hallucinations. In this method, zolpidem is extracted from blood or other biological fluids/tissues using solid phase extraction technology for analysis. The extract is then assayed using selected ion monitoring gas chromatography/mass spectrometry for absolute confirmation of the compound. The quantitation of this drug is made from standard curves constructed using selected ion monitoring and peak-area ratios of analyte vs. internal standard of quantifying ions.

Identification and quantitation of zopiclone in biological matrices using gas chromatography-mass spectrometry (GC-MS).

Zopiclone is a nonbenzodiazapine hypnotic used for the treatment of insomnia. Significant side effects include daytime drowsiness, dizziness, lightheadedness, bitter taste, dry mouth, headache, and upset stomach. A single method for confirmation and quantitation of zopiclone was developed for biological specimens and tissues. Zopiclone is extracted from the biological matrix using solid phase extraction technology. The drug is confirmed using gas chromatography mass spectrometry for toxicological and forensic purposes.

Zolpidem : Forensic aspects for the toxicologist and pathologist.

Zolpidem (Ambien), a nonbenzodiazepine hypnotic, is indicated for the short-term treatment of insomnia. Because it has become the most widely prescribed sleep aid in the United States, it is being increasingly detected in a variety of forensic specimens, and its interaction with other medications is being questioned. We present a comprehensive overview of the basic chemistry, pharmacokinetics, and pharmacodynamics of zolpidem; its interaction with other prescription drugs; its effects on driving and motor skills; and its analysis and interpretation in forensic casework.

A sertraline-intoxicated driver.

Sertraline is a selective serotonin reuptake inhibitor (SSRI) that is chemically unrelated to other SSRIs, tricyclic antidepressants, and other currently available antidepressant medications. This report documents a case of driving under the influence of sertraline. The subject was involved in a motor vehicle accident. Upon contact by law enforcement, the subject was confused and could neither stand nor walk. The officer noted mumbled speech, droopy eyes, and that the subject seemed sleepy. No alcohol was present in the vehicle, and no odor of alcohol was detected on the subject's breath. The subject was determined to be under the influence of some intoxicating substance. Toxicological analysis revealed only the presence of sertraline. Sertraline was extracted from the blood sample utilizing solid-phase extraction and identified and quantitated by gas chromatography-mass spectrometry. The blood sertraline concentration was determined to be 1285 microg/L.

The determination of morphine in urine and oral fluid following ingestion of poppy seeds.

In workplace drug-testing programs, the use of heroin, morphine, and codeine is currently determined by the analysis of urine specimens. It has been shown that ingestion of poppy seeds can cause a positive test result for morphine. In an attempt to differentiate positive results caused by poppy seed ingestion from those caused by heroin or morphine abuse, the screening cutoff concentration for urine opiates in the federal workplace drug-testing program was raised to 2000 ng/mL from 300 ng/mL. Currently, oral fluid is under consideration as a possible alternative to urine for drug testing. The suggested cutoff for oral fluid morphine is 40 ng/mL; however, the effect of poppy seed ingestion on morphine concentrations in this specimen type has not been widely investigated. Volunteers at two separate sites ingested commercially available poppy seeds and/or poppy seed bagels. Oral fluid and urine samples were collected at both sites. Oral fluid samples were collected for 24 h; urine was collected for 2 days. The samples were analyzed for the presence of codeine and morphine using gas chromatography-mass spectrometry. Morphine concentrations greater than the suggested cutoff concentrations were detected in oral fluid up to 1 h and in urine for up to 8 h. This study has demonstrated that a positive result for morphine in oral fluid may be due to the ingestion of poppy seeds.

The analysis and distribution of mescaline in postmortem tissues.

Mescaline (3,4,5-trimethoxyphenethylamine) is a hallucinogenic alkaloid found in the peyote cactus. This report documents mescaline distribution in a death caused by multiple gunshot wounds. Mescaline was extracted with a butyl chloride liquid-liquid method and identified by mass spectrometry. Quantitative analysis was performed by gas chromatography using a nitrogen-phosphorus detector. Concentrations of the drug were 2.95 mg/L, 2.36 mg/L, 8.2 mg/kg, and 2.2 mg/kg in blood, vitreous, liver, and brain, respectively.