-
Clinical Toxicology (Philadelphia, Pa.) Sep 2022Novel opioids in the illicit drug supply, such as the "nitazene" group of synthetic opioids, present an ongoing public health problem due to high potency and respiratory...
BACKGROUND
Novel opioids in the illicit drug supply, such as the "nitazene" group of synthetic opioids, present an ongoing public health problem due to high potency and respiratory depressant effects. We describe three patients in whom -piperidinyl etonitazene, a compound not previously reported in human exposure, was detected after suspected opioid overdose. Other substances that these patients tested for included fentanyl, cocaine, levamisole, phenacetin, benzoylecgonine, -fluorofentanyl, presumptive heroin (tested as 6-monoacetylmorphine (6-MAM), morphine, and codeine), and tramadol.
METHODS
This is a case series of patients with acute opioid overdose enrolled in an ongoing multicenter prospective cohort study. Data collected included reported substance use, clinical course, naloxone dose and response, outcome, and analytes detected in biological samples.
RESULTS
Between October 6, 2020 and October 31, 2021, 1006 patients were screened and 412 met inclusion criteria. Of these, three patients (age 33-55) tested positive for -piperidinyl etonitazene at one site in New Jersey over a period of three days in July 2021. Two patients reported the use of cocaine; one reported the use of heroin and alprazolam. All three patients received naloxone with improvement in their mental status (2 milligrams (mg) intranasally (IN); 8 mg IN; 0.08 mg intravenous (IV)). Two of three received subsequent doses for recurrence of opioid toxicity (0.4-0.6 mg IV). One patient was diagnosed with pneumonia and admitted to the intensive care unit, one was discharged from the Emergency Department (ED), and one used additional drug while in the ED and required admission for a naloxone infusion. None developed organ damage or sequelae.
CONCLUSION
These cases represent a local outbreak of a novel "nitazene" opioid. Public health toxicosurveillance should incorporate routine testing of this emerging class of synthetic compounds in the illicit drug supply.
Topics: Adult; Alprazolam; Analgesics, Opioid; Benzimidazoles; Cocaine; Codeine; Drug Overdose; Fentanyl; Heroin; Humans; Illicit Drugs; Levamisole; Middle Aged; Naloxone; Narcotic Antagonists; Opiate Overdose; Phenacetin; Prospective Studies; Tramadol
PubMed: 35708103
DOI: 10.1080/15563650.2022.2084406 -
Drug and Alcohol Dependence Dec 2019Drug checking is a harm reduction intervention that allows for identification of drug composition. The objective of the study was to assess drug market components and...
OBJECTIVES
Drug checking is a harm reduction intervention that allows for identification of drug composition. The objective of the study was to assess drug market components and concordance between expected substance reported by clients and results from point-of-care drug checking at music festivals and events in British Columbia.
METHODS
From July to September 2018, we provided drug checking services at four events using combination Fourier Transform Infrared (FTIR) spectroscopy and fentanyl immunoassay strips. We measured concordance between expected substance as reported by clients to the results from the FTIR/fentanyl immunoassay strip and tracked unexpected adulterants.
RESULTS
In total, 336 checks were completed. Most samples were expected by clients to be psychedelics (69.3%) or stimulants (19.6%). Of the 233 psychedelic samples, 169 (72.5%) contained the expected, unadulterated substance, and 27 (11.6%) contained additional contaminants. Of 66 stimulant samples, 41 (62.1%) contained expected substance, while 24 (36.4%) contained additional contaminants. Unexpected adulterants such as fentanyl, levamisole, and phenacetin were also found, in addition to several novel psychoactive substances.
DISCUSSION
We found a large proportion of substances that contained unexpected adulterants. Our findings highlight the value of continued drug checking and will be helpful in designing future harm reduction interventions in similar contexts.
Topics: British Columbia; Central Nervous System Stimulants; Drug Contamination; Fentanyl; Hallucinogens; Harm Reduction; Holidays; Humans; Illicit Drugs; Immunoassay; Levamisole; Music; Phenacetin; Reproducibility of Results; Spectroscopy, Fourier Transform Infrared; Substance Abuse Detection
PubMed: 31605958
DOI: 10.1016/j.drugalcdep.2019.107589 -
Talanta Apr 2021MIL-101(Cr) and graphene aerogel (GA) were hybridized as a multifunctional adsorbent for the preconcentration of trace analytes. The novel MIL-101(Cr)@GA was prepared...
MIL-101(Cr) and graphene aerogel (GA) were hybridized as a multifunctional adsorbent for the preconcentration of trace analytes. The novel MIL-101(Cr)@GA was prepared and characterized by FTIR, XRD and SEM, where GA is serving as a carrier for MIL-101(Cr). The synthesized composite as a solid phase extraction (SPE) sorbent combined with UPLC-MS/MS was applied for the determination and quantification of five NSAIDs (phenacetin, meloxicam, naproxen, diclofenac sodium and carprofen) in different environmental water samples. The parameters influencing the whole extraction process were systematically optimized. Under the most favorable. conditions, good sensitivity was achieved with a limit of detection between 0.006 and 0.012 ng mL, the linear range of 0.02-2 ng mL for phenacetin, meloxicam and 0.05-5 ng mL for naproxen, diclofenac sodium, carprofen (r ≥ 0.9940). The satisfactory recoveries of the target analytes were in the range from 77.2 to 103.3% with relative standard deviation (RSD) from 0.6% to 8.4%. The established method was proved to be simple, highly sensitive and accurate. The adsorbent could be reusable up to nine cycles without any decrease in performance, which provides economic strategy and little waste generation. Adsorption behaviors were explored by choosing two typical types of NSAIDs as models to measure the adsorption capacity of MIL-101(Cr)@GA. The maximum adsorption capacities for PHE and NAP were 232.5 and 333.3 mg g, respectively.
Topics: Adsorption; Anti-Inflammatory Agents, Non-Steroidal; Chromatography, High Pressure Liquid; Chromatography, Liquid; Graphite; Metal-Organic Frameworks; Solid Phase Extraction; Tandem Mass Spectrometry; Water; Water Pollutants, Chemical
PubMed: 33592689
DOI: 10.1016/j.talanta.2020.121846 -
Mutation Research. Genetic Toxicology... Nov 2019I first became acquainted with the Ames test at the very beginning of my career in 1978, when my task at the National Institute of Health Sciences (Tokyo) was to screen...
I first became acquainted with the Ames test at the very beginning of my career in 1978, when my task at the National Institute of Health Sciences (Tokyo) was to screen for mutagenicity of food additives used in Japan, using the Ames test. I also used this test to research the metabolic activation mechanisms of chemical carcinogens, in particular, the analgesic drug, phenacetin. This chemical was not mutagenic in Salmonella typhimurium TA100 with standard 9000 × g supernatant of liver homogenates (S9) from rat but was mutagenic with hamster S9. It was revealed that hamster S9 had much higher deacetylation activities than rat S9, which accounts for the species difference. Then, my work was focused on molecular biology. We cloned the genes encoding nitroreductase and acetyltransferase in Salmonella typhimurium TA1538. Plasmids carrying these genes made strain TA98 more sensitive to mutagenic nitroarenes and aromatic amines. Because of their high sensitivity, the resulting strains such as YG1021 and YG1024 are widely used to monitor mutagenic nitroarenes and aromatic amines in complex mixtures. Later, we disrupted the genes encoding DNA polymerases in TA1538 and classified chemical mutagens into four classes depending on their use of different DNA polymerases. I was also involved in the generation of gpt delta transgenic rodent gene mutation assays, which examine the results of the Ames test in vivo. I have unintentionally developed my career under the influence of Dr. Ames and I would like to acknowledge his remarkable achievements in the field of environmental mutagenesis and carcinogenesis.
Topics: Activation, Metabolic; Animals; Animals, Genetically Modified; Animals, Inbred Strains; Bacterial Proteins; Boston; Carcinogens; Cloning, Molecular; Cricetinae; DNA-Directed DNA Polymerase; Environmental Exposure; Escherichia coli; Escherichia coli Proteins; Female; Food Additives; Japan; Mice; Microsomes, Liver; Mutagenicity Tests; Mutagens; Pentosyltransferases; Rats; Recombinant Proteins; Salmonella typhimurium
PubMed: 31699345
DOI: 10.1016/j.mrgentox.2019.503095 -
Journal of Pharmaceutical and... Jun 2024Street cocaine is often mixed with various substances that intensify its harmful effects. This paper proposes a framework to identify attenuated total reflection Fourier...
Street cocaine is often mixed with various substances that intensify its harmful effects. This paper proposes a framework to identify attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR) intervals that best predict the concentration of adulterants in cocaine samples. Wavelengths are ranked according to their relevance through ReliefF and mRMR feature selection approaches, and an iterative process removes less relevant wavelengths based on the ranking suggested by each approach. Gaussian Process (GP) regression models are constructed after each wavelength removal and the prediction performance is evaluated using RMSE. The subset balancing a low RMSE value and a small percentage of retained wavelengths is chosen. The proposed framework was validated using a dataset consisting of 345 samples of cocaine with different amounts of levamisole, caffeine, phenacetin, and lidocaine. Averaged over the four adulterants, the GP regression coupled with the mRMR retained 1.07 % of the 662 original wavelengths, outperforming PLS and SVR regarding prediction performance.
PubMed: 38889578
DOI: 10.1016/j.jpba.2024.116294 -
Toxicology in Vitro : An International... Mar 2022Hydroxygenkwanin (HGK), a natural flavonoid extracted from the buds of Daphne genkwa Sieb.et Zucc. (Thymelaeaceae), possesses a wide range of pharmacological activities,...
Hydroxygenkwanin (HGK), a natural flavonoid extracted from the buds of Daphne genkwa Sieb.et Zucc. (Thymelaeaceae), possesses a wide range of pharmacological activities, including anti-inflammatory, antibacterial and anticancer. However, the inhibitory effect of HGK on cytochrome P450 (CYP) remains unclear. This study investigated the potential inhibitory effects of HGK on CYP1A2, 2B1/6, 2C9/11, 2D1/6, 2E1 and 3A2/4 enzymes in human and rat liver microsomes (HLMs and RLMs) by the cocktail approach. HGK exhibited no time-dependent inhibition of CYP activities in HLMs and RLMs. Enzyme inhibition kinetics indicated that HGK was not only a competitive inhibitor of human CYP1A2 and 2C9, but also competitively inhibited rat CYP1A2 and 2C11 activities, with K value at 0.84 ± 0.03, 8.09 ± 0.44, 2.68 ± 0.32 and 8.35 ± 0.31 μM, respectively. Further studies showed that the inhibitory effect of HGK on CYP enzymes was weaker than that of diosmetin, which may be related to the substitution of hydroxyl and methoxy in the A and B rings of the flavone skeleton. Therefore, the low K values of HGK for CYP1A2 and 2C may lead to potential drug-drug interactions and toxicity.
Topics: Animals; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drug Interactions; Flavonoids; Humans; Isoenzymes; Kinetics; Male; Microsomes, Liver; Rats; Rats, Sprague-Dawley; Risk Assessment
PubMed: 34843882
DOI: 10.1016/j.tiv.2021.105281 -
Forensic Science International Oct 2021Cocaine is a naturally occurring psychostimulant drug available worldwide. Drug trafficking networks adulterate pure cocaine with cutting agents to increase their...
Cocaine is a naturally occurring psychostimulant drug available worldwide. Drug trafficking networks adulterate pure cocaine with cutting agents to increase their earnings. This study presents a descriptive statistical analysis of the cutting agents found in 2118 cocaine samples that were seized in the Northern Region of Colombia (in the period 2015-2017). The data used in this study was drawn from the GC-MS analytical reports of the National Institute of Legal Medicine and Forensic Sciences -Colombia, Northern Region. Results showed diverse cutting agents in seized cocaine samples, from which the most commonly used are caffeine, phenacetin, lidocaine, imidazole and levamisole. In addition, cocaine samples showed different mixtures of the above cutting agents, predominantly caffeine/phenacetin and caffeine/lidocaine/phenacetin mixtures.
Topics: Aporphines; Caffeine; Cocaine; Codeine; Colombia; Drug Contamination; Drug Trafficking; Humans; Imidazoles; Levamisole; Lidocaine; Phenacetin; Spatio-Temporal Analysis; Tetramisole
PubMed: 34450541
DOI: 10.1016/j.forsciint.2021.110911 -
Drug Design, Development and Therapy 2020Calycosin (CAL), a type of O-methylated isoflavone extracted from the herb (AM), is a bioactive chemical with antioxidative, antiphlogistic and antineoplastic...
BACKGROUND
Calycosin (CAL), a type of O-methylated isoflavone extracted from the herb (AM), is a bioactive chemical with antioxidative, antiphlogistic and antineoplastic activities commonly used in traditional alternative Chinese medicine. AM has been shown to confer health benefits as an adjuvant in the treatment of a variety of diseases.
AIM
The main objective of this study was to determine whether CAL influences the cytochrome P450 (CYP450) system involved in drug metabolism.
METHODS
Midazolam, tolbutamide, omeprazole, metoprolol and phenacetin were selected as probe drugs. Rats were randomly divided into three groups, specifically, 5% Carboxymethyl cellulose (CMC) for 8 days (Control), 5% CMC for 7 days + CAL for 1 day (single CAL) and CAL for 8 days (conc CAL), and metabolism of the five probe drugs evaluated using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).
RESULTS
No significant differences were observed for omeprazole and midazolam, compared to the control group. and t values of only one probe drug, phenacetin, in the conc CAL group were significantly different from those of the control group ( h: 0.50±0.00 vs 0.23±0.15; control vs conc CAL). of tolbutamide was decreased about two-fold in the conc CAL treatment group (conc vs control: 219.48 vs 429.56, <0.001).
CONCLUSION
Calycosin inhibits the catalytic activities of CYP1A2, CYP2D6 and CYP2C9. Accordingly, we recommend caution, particularly when combining CAL as a modality therapy with drugs metabolized by CYP1A2, CYP2D6 and CYP2C9, to reduce the potential risks of drug accumulation or ineffective treatment.
Topics: Animals; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Drugs, Chinese Herbal; Isoflavones; Medicine, Chinese Traditional; Metoprolol; Midazolam; Omeprazole; Phenacetin; Rats; Tolbutamide
PubMed: 32099327
DOI: 10.2147/DDDT.S236221 -
Frontiers in Pharmacology 2020Vonoprazan fumarate is a potassium-competitive acid blocker that was developed as a novel acid-suppressing drug for multiple indications. As a potential alternative to...
BACKGROUND
Vonoprazan fumarate is a potassium-competitive acid blocker that was developed as a novel acid-suppressing drug for multiple indications. As a potential alternative to proton-pump inhibitors, the determination of the drug-drug interactions is vital for further applications. Probe drug cocktails are a type of rapid, economical, and efficient approach for evaluating cytochrome P450 enzyme activities. Since vonoprazan is metabolized partly by cytochrome P450, cocktails were used to study CYP-based drug-drug interactions.
METHODS
This study was conducted both and . In the study of rat liver microsomes, ultra-performance liquid chromatography coupled to tandem mass spectrometry was utilized to assess the reversible inhibition of cytochrome P450 by vonoprazan by determining the concentration of probe drugs (phenacetin, bupropion, tolbutamide, dextromethorphan, midazolam, chlorzoxazone). The differences in the levels of probe drugs between the rat groups with or without vonoprazan administration were also tested in the rats.
RESULTS
analysis revealed that the IC values of midazolam, tolbutamide, dextromethorphan, and bupropion in rat microsomes were 22.48, 18.34, 3.62, and 3.68 μM, respectively, while chlorzoxazone and phenacetin displayed no inhibition. analysis revealed that midazolam, bupropion, dextromethorphan, and tolbutamide showed significant ( < 0.05) differences in distinct pharmacokinetic parameters after vonoprazan administration, while those of chlorzoxazone and phenacetin were not significantly different.
CONCLUSION
The and results indicated that vonoprazan can inhibit CYP3A4, CYP2C9, CYP2D6, and CYP2B6, suggesting that the coadministration of vonoprazan with cytochrome P450 substrates should be performed cautiously in clinical settings.
PubMed: 32116727
DOI: 10.3389/fphar.2020.00053 -
Analytical Methods : Advancing Methods... Jun 2020A new method, simple and fast, for fluconazole (FLU) quantification in cerebrospinal fluid (CSF) samples using dispersive liquid-liquid microextraction (DLLME) and an...
Dispersive liquid-liquid microextraction followed by green high-performance liquid chromatography for fluconazole determination in cerebrospinal fluid with the aid of chemometric tools.
A new method, simple and fast, for fluconazole (FLU) quantification in cerebrospinal fluid (CSF) samples using dispersive liquid-liquid microextraction (DLLME) and an eco-friendly mobile phase for HPLC-PDA was developed. The study of DLLME extraction condition covered the investigation of 12 combinations of extraction and disperser solvents followed by a fractional factorial design 2(7-3) to determine the influence of seven factors. After this stage, a central composite design was performed for three factors and a response surface was obtained. Aiming a compromise between a good recovery and a low organic solvent use it was established an extraction condition that consists of: 100 μL of chloroform, 100 μL of isopropyl alcohol, 200 μL of CSF, 200 μL of 50 mM phosphate buffer pH 7.3 and centrifugation for 5 min at 2200g and 4 °C. The HPLC analysis used an Ascentis® Express C18 column (100 mm × 4.6 mm, 2.7 μm) and an Ascentis® Express C18 guard column (3 mm × 4.6 mm, 2.7 μm), ethanol : water (15 : 85, v/v) as mobile phase, temperature of 45 °C, flow rate of 0.8 mL min-1 and phenacetin as internal standard. The method validation was performed according to European Agency's Guideline on Bioanalytical Validation Methodology and a linear range was obtained from 0.25 to 62.5 μg mL-1, with precision and accuracy within the recommended limits and recovery of 70% for FLU and 81% for phenacetin. Samples were stable in the studies performed and the method showed to be selective and with no carryover effect. The feasibility of the obtained method was confirmed by FLU determination at a CSF from a patient who was treated for neuromycosis. Therefore, here is described a method that meets many principles of green analytical chemistry and is useful for FLU therapeutic monitoring.
Topics: Chloroform; Chromatography, High Pressure Liquid; Fluconazole; Humans; Liquid Phase Microextraction; Solvents
PubMed: 32930170
DOI: 10.1039/d0ay00704h