Presence Of Other Drugs Research Articles

B-290 Static Analytical Scopes and Lab Processes - An Existing Public Health Hazard

Abstract Background Most chromatographic-based procedures have defined analytical scopes. This allows for laboratories to include the most relevant analytes in test panels and for care providers to know exactly what is included and excluded in ordered tests. Analytical scopes can be developed based on drug trend data, consensus body recommendations, or mandatory guidelines. However, it is reasonable to conclude that strictly adhering to these scopes, or not having robust processes in place that permit for rapid scope changes, will result in the underreporting of drug use in a population or miss a relevant drug finding for a single patient. For example, SAMHSA’s minimum mandatory guidelines for urine workplace drug testing does not include fentanyl. While true the number of fentanyl positive cases that are missed in this population is speculative, a factual case in point is made by evaluating laboratory results for a major novel psychoactive substance (NPS) drug class - designer benzodiazepines (DB). We performed a retrospective review to study the frequency that designer benzodiazepines would have been missed in reporting without further intervention by laboratory staff. Methods Blood samples were screened by ELISA and LC-TOF/MS. Confirmation testing using two different LC-MS/MS panels was conducted on samples that screened presumptive positive for benzodiazepines. Analytical results were retrieved from the laboratory’s data management system using the following criteria: a) date range: Feb 2023 to Feb 2024, b) blood matrix, c) DUID testing cases where benzodiazepine screening was performed by ELISA and by LC-TOF/MS, and d) at least one DB was reported regardless of the presence of other drugs. Results Nine parent DB or their metabolites were identified in the 46 cases in this study: 8-aminoclonazolam (n=3), alpha-hydroxyetizolam (n=2), bromazolam (n=35), clonazolam (n=2), deschloroetizolam (n=1), etizolam (n=1), flubromazolam (n=7), flualprazolam (n=1), and pyrazolam (n=1). Benzodiazepine screening by ELISA and LC-TOF/MS was positive for 45 and 46 cases, respectively. In the 45 cases that screened positive by ELISA, 41 did not confirm positive for any classical benzodiazepine (CBZ) which included alprazolam, diazepam, lorazepam, clonazepam, temazepam, oxazepam, and the nordiazepam metabolite. Only 4 cases tested positive for both a DB and CBZ (alprazolam or clonazepam) simultaneously. Conclusions While it is understood that defined analytical scopes are a laboratory necessity, care providers, law enforcement, public policy decision makers, and communities at large need to understand the limitations and regulations surrounding analytical test procedures. For some testing, a laboratory is obligated to follow mandatory guidelines, but from a clinical or medicolegal perspective, the risk is two-fold. The first is that the causative drug producing any untoward effects goes unrecognized. The second is that symptoms displayed are attributed to the presence of other drugs. This work stresses the importance of sincere collaboration between laboratories and entities that are responsible for analytical scope development and providing funding to ensure the appropriateness of real-time drug surveillance and reporting efforts.

Detection of Amisulpride Using a Chromium-Salophen Optical Probe

Patients with psychosis around the world are routinely prescribed anti-psychotic medications. Amisulpride (AMI) is one such medication. In order to detect cases like drug overdose, drug abuse, or intentional poisoning, simple, selective and sensitive probes are required. In the present work, we have synthesized a fluorescent probe (CRSA) for detecting Amisulpride (AMI) and characterized it by FT-IR, NMR and mass spectroscopy. The probe emits green light in ethanol and acts as a “turn-off” luminescent sensor for the anti-psychotic drug Amisulpride (AMI) with a quenching percentage of 94% and an excellent limit of detection of 1.6 μM. The sensor responded effectively to only AMI even in the presence of other drugs like sertraline, fluoxetine, escitalopram, paroxetine, olanzapine and clozapine ensuring good selectivity and specificity of the method. The effect of pH on the sensing abilities CRSA and the applicability of the method to real-life samples were also studied using spiked alcohol samples.

Selective detection of azelnidipine in pharmaceuticals via carbon dot mediated spectrofluorimetric method: A green approach.

A spectrofluorimetric method using fluorescent carbon dots (CDs) was developed for the selective detection of azelnidipine (AZEL) pharmaceutical in the presence of other drugs. In this study, N-doped CDs (N-CDs) were synthesized through a single-step hydrothermal process, using citric acid and urea as precursor materials. The prepared N-CDs showed a highly intense blue fluorescence emission at 447 nm, with a photoluminescence quantum yield of ~21.15% and a fluorescence lifetime of 0.47 ns. The N-CDs showed selective fluorescence quenching in the presence of all three antihypertensive drugs, which was used as a successful detection platform for the analysis of AZEL. The photophysical properties, UV-vis light absorbance, fluorescence emission, and lifetime measurements support the interaction between N-CDs and AZEL, leading to fluorescence quenching of N-CDs as a result of ground-state complex formation followed by a static fluorescence quenching phenomenon. The detection platform showed linearity in the range 10-200 μg/ml (R2 = 0.9837). The developed method was effectively utilized for the quantitative analysis of AZEL in commercially available pharmaceutical tablets, yielding results that closely align with those obtained from the standard method (UV spectroscopy). With a score of 0.76 on the 'Analytical GREEnness (AGREE)' scale, the developed analytical method, incorporating 12 distinct green analytical chemistry components, stands out as an important technique for estimating AZEL.

Study Of Oral Antihypertension Drug Interactions On Prescribing Geriatric Patients With Hypertension Disease In Outpatient Installations Wilujeng Hospital In The 2021 Period

Drug interactions are changes in the effectiveness or toxicity of one drug due to the presence of other drugs given simultaneously. Drugs that are often involved in potential interactions are drugs that are used daily for the clinical management of elderly patients with chronic diseases. The aim of this study is to determine the incidence of antihypertensive drug interactions in an effort to reduce the incidence of interactions between drugs in elderly patients (Geriatrics). ). Observational descriptive research with a cross-sectional research design with a quantitative approach and a retrospective sampling method in geriatric outpatients with a diagnosis of hypertension and data obtained using statistical methods by calculating the percentage of each part to be analyzed including a general description of antihypertensive drug prescribing. then whether or not there are drug interactions with patient prescriptions at Wilujeng Hospital. The results of the research show that drug interactions at Wilujeng Hospital for the 2021 period showed that the highest number of interactions occurred between hypertension drugs, namely furosemde and ramipril, where 14 incidents occurred or (14%), the interaction that occurred between furosemide and ramipril was synergistic pharmacodynamics. , and the highest use of antihypertensive drugs is amlodipine 43%; furosemide 12%; spironolactone 8%; valsartan 2%; bisoprolol 6%; candesartan 3%; ramipril 5%; captopril11%;hydrocholotiazide4%;irbesartan2%;verapamil2%andpropranolol2%.

Validation of HPLC-DAD method for analysis of paracetamol and potassium sorbate in liquid oral formulations and its application to forced degradation study

AbstractDue to the frequent use of paracetamol formulations, it is useful to develop an analytical technique for the determination of intact paracetamol in presence of other drugs and excipients or the degradation products. In this study, a simple, isocratic, fast, specific, accurate and precise stability-indicating high performance liquid chromatography (HPLC) method has been developed and validated for simultaneous quantitative determination of paracetamol (PCM) and potassium sorbate (PS) in oral liquid formulations. The chromatographic separation was achieved on Zorbax SB C18 column (150 × 4.6 mm, 5 µm) with Zorbax SB C18 precolumn (12.5 × 4.6 mm, 5 µm) using distilled water pH 2 with ortho-phosphoric acid and acetonitrile (70:30, v/v) as a mobile phase, and UV detection at 235 nm. The temperature of the column was kept constant at 25 °C. The method was validated according to International Conference on harmonization (ICH) guidelines. The method demonstrated excellent linearity, with a correlation coefficient of 0.9996 and 0.9998 for PCM and PS, respectively, over the concentration ranges of 10–600 μg mL−1 (PCM) and 6–500 μg mL−1 (PS). The retention time was found to be 1.98 and 4.86 min for PCM and PS, respectively. Oral liquid formulation samples were subjected to various stress conditions (acidic and alkaline hydrolysis, as well as oxidative, heat and photolytic degradation) for the purpose of forced degradation study. The major degradation of paracetamol was achieved in acidic and basic stress conditions, while thermal and photolytic degradation generally had the least influence. On the other hand, potassium sorbate was highly susceptible to photolytic degradation. It was also shown that the formulation has strong influence on stability of tested compounds. Forced degradation studies demonstrated the stability-indicating power of the method and can be used to assess the stability of paracetamol and potassium sorbate in oral liquid formulations.

An Overview of Biosynthetic Pathway and Therapeutic Potential of Naringin

Abstract: Naringin is a naturally obtained chemical from plants that is formed as a secondary metabolite in them. It possesses significant properties that are useful to humans. The primary sources of naringin extract include fruits of the citrus family which are Citrus reticulata, Citrus bergamia, Citrus aurantium, and Citrus paradisi. It belongs to a class of alcohols primarily consisting of a fused ring system which is responsible for its different medicinal properties, as a consequence, it is widely used in the nutraceutical market nowadays. Nutraceuticals are a part of food that provides health benefits by giving supplements to the body; their final extract form is white in color having crystalline properties with a melting point of 83oC and solubility of 1 mg/ml at 40oC. The absorption of nutraceuticals occurs inside the stomach as it requires a specific pH range between 3.5-4.2. After absorption, it gets converted into naringenin in the liver via a cascade of reactions like dehydrogenation, acetylation, and hydrolysis. Several enzymes are responsible for its conversion into an active form which includes cytochrome P-450, and chalcone isomerase. Its bioavailability depends on a variety of factors including disease condition, gastric moiety, pH of absorption site, the presence of other drugs, and many more. It gets metabolized in the liver itself and finally excreted in the urine. It can be tolerated by the body at high doses, but other conditions can cause its toxicity inside the human body. Its primary properties include anti-inflammatory actions, anti-aging properties, antibacterial properties, anti-cancer properties, and obesity issues.

Label-free SERS assay combined with multivariate spectral data analysis for lamotrigine quantification in human serum

Considering the need for a more time and cost-effective method for lamotrigine (LTG) detection in clinics we developed a fast and robust label-free assay based on surface-enhanced Raman scattering (SERS) for LTG quantification from human serum. The optimization and application of the developed assay is presented showing the: (i) exploration of different methods for LTG separation from human serum; (ii) implementation of a molecular adsorption step on an ordered Au nanopillar SERS substrate; (iii) adaptation of a fast scanning of the SERS substrate, performed with a custom-built compact Raman spectrometer; and (iv) development of LTG quantification methods with univariate and multivariate spectral data analysis. Our results showed, for the first time, the SERS-based characterization of LTG and its label-free identification in human serum. We found that combining a miniaturized solid phase extraction, as sample pre-treatment with the SERS assay, and using a multivariate model is an optimal strategy for LTG quantification in human serum in a linear range from 9.5 to 75 μM, with LoD and LoQ of 3.2 μM and 9.5 μM, respectively, covering the suggested clinical therapeutic window. We also showed that the developed assay allowed for quantifying LTG from human serum in the presence of other drugs, thereby demonstrating the robustness of label-free SERS. The sensing approach and instrumentation can be further automated and integrated in devices that can advance the drug monitoring in real clinical settings.Graphical abstract

Novel disposable and portable 3D-printed electrochemical apparatus for fast and selective screening of 25E-NBOH in forensic samples

The advent of new psychoactive substances (NPS) has caused enormous difficulty for legal control since they are rapidly commercialized, and their chemical structures are routinely altered. In this aspect, derivatives phenethylamines, such as 25E-NBOH, have received great attention in the forensic scenario. Hence, we propose portable and cost-effective (U$ 5.00) 3D-printed devices for the electrochemical screening of 25E-NBOH for the first time. The cell and all electrodes were printed using acrylonitrile butadiene styrene filament (insulating material) and conductive filament (graphite embedded in a polylactic acid matrix), respectively, both by the fused deposition modeling (FDM) 3D printing technique. The electrochemical apparatus enables micro-volume analysis (50–2000 μL), especially important for low sample volumes. A mechanistic route for the electrochemical oxidation of 25E-NBOH is proposed based on cyclic voltammetric data, which showed two oxidation processes around +0.75 V and +1.00 V and a redox pair between +0.2 and −0.2 V (vs. graphite ink pseudo-reference). A fast and sensitive square-wave voltammetry method was developed, which exhibited a linear working range from 0.85 to 5.1 μmoL−1, detection limit of 0.2 μmol L−1, and good intra-electrode precision (n = 10, RSD <5.3 %). Inter-electrode measurements (n = 3, RSD <9.8 %) also attested that the electrode production process is reproducible. Interference tests in the presence of other drugs frequently found in blotting paper indicated high selectivity of the electrochemical method for screening of 25E-NBOH. Screening analysis of blotting paper confirmed the presence of 25E-NBOH in the seized samples. Moreover, a recovery percentage close to 100 % was found for a spiked saliva sample, suggesting the method's usefulness for quantitative purposes aimed at information on recent drug use.

Biochemical differences between high and low dose methadone clients on stable maintenance therapy

The methadone dose required to prevent withdrawal symptoms in chronic methadone users varies dramatically from 5 to 300 mg/day, which could be attributed to a number of biochemical factors, including human µ-opioid receptor (hMOR) density, down-stream desensitization, concurrent drug use or P-glycoprotein (P-gp) expression, or other, possibly genetic factors. Here we describe some biochemical changes of patients taking higher versus lower doses in chronic methadone maintenance therapy (MMT). hMOR density was measured in leukocytes from methadone-maintained patients receiving lower dose (&lt;100 mg/day) or higher dose (≥100 mg/day) and naive subjects by flow cytometry. Desensitization of receptor signaling was examined by measuring in vivo and attenuated cyclic AMP (cAMP) levels in response to increasing methadone concentrations. P-gp expression and the presence of other drugs were measured using validated methods.

Optical detection of scopolamine and ketamine with a BODIPY-Phen conjugate and Cu(II)

Chemical submission is becoming a global growing threat. Therefore, the development of fast and reliable methods for detecting the presence of chemical submission drugs in drinks is of great interest. For this purpose, a new BODIPY-Phen conjugate consisting of a 1,10-phenanthroline moiety connected through its 4-position to the meso position of a BODIPY dye has been synthesized and characterized by NMR, UV–vis spectroscopy and by single-crystal X-ray diffraction. BODIPY-Phen in combination with Cu(II) was used as a probe for the fluorescent and colorimetric detection of scopolamine and ketamine, two of the drugs used in cases of chemical submission. The determined limits of detection in water were 3 μM for scopolamine and 2.88 μM for ketamine. Selectivity of the probe in the presence of other drugs and some possible interferents that could be found in beverages has also been tested. The detection process seems to be due to a reduction of the Cu(II) ion to Cu(I) followed by coordination of Cu(I) to the BODIPY-Phen conjugate, which results in quenching of its fluorescence together with a visible color change. The probe is able to detect by the unaided eye the presence of scopolamine in real soft drinks and alcoholic beverages spiked with the drug.

Biomass-Derived Core-Shell Carbon Dots with Embedded Tripodal Receptors for the Selective Recognition of Mefenamic Acid in Pharmaceutical Formulations and Urine.

A tripodal amine (TPA) with -OH, N, and S donors is synthesized to functionalize a core-shell carbon dot composite (FCDs@SiO2-TPA) for sensing application. The TPA is characterized by spectroscopic and spectrometric techniques, and the composite is characterized by Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), Brunauer-Emmett-Teller (BET), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy-dispersive X-ray spectra (EDS) techniques. The composite has the ability to recognize mefenamic acid (MFA) selectively even in the presence of other drugs like ibuprofen sodium, acetylsalicylic acid, naproxen sodium, diclofenac sodium, and ketoprofen. It can also be used for the quantification of MFA by recording the emission quenching response of the sample at λexc. = 350 nm and λems. = 460 nm (linear range = 1-8 μM and LOD = 197 nM). The density functional theory calculations and 1H NMR titration suggest quenching of the emission signal due to photoinduced electron transfer via hydrogen bonding between the probe and MFA. The composite FCDs@SiO2-TPA has been demonstrated as a reliable and cost-effective sensing probe for the detection of MFA in pharmaceutical formulations, water samples, and cow urine samples.

Instant Detection of Synthetic Cannabinoids on Physical Matrices, Implemented on a Low-Cost, Ultraportable Device.

Synthetic cannabinoids (SCs) make up a class of novel psychoactive substances (NPS), used predominantly in prisons and homeless communities in the U.K. SCs can have severe side effects, including psychosis, stroke, and seizures, with numerous reported deaths associated with their use. The chemical diversity of SCs presents the major challenge to their detection since approaches relying on specific molecular recognition become outdated almost immediately. Ideally one would have a generic approach to detecting SCs in portable settings. The problem of SC detection is more challenging still because the majority of SCs enter the prison estate adsorbed onto physical matrices such as paper, fabric, or herb materials. That is, regardless of the detection modality used, the necessary extraction step reduces the effectiveness and ability to rapidly screen materials on-site. Herein, we demonstrate a truly instant generic test for SCs, tested against real-world drug seizures. The test is based on two advances. First, we identify a spectrally silent region in the emission spectrum of most physical matrices. Second, the finding that background signals (including from autofluorescence) can be accurately predicted is based on tracking the fraction of absorbed light from the irradiation source. Finally, we demonstrate that the intrinsic fluorescence of a large range of physical substrates can be leveraged to track the presence of other drugs of interest, including the most recent iterations of benzodiazepines and opioids. We demonstrate the implementation of our presumptive test in a portable, pocket-sized device that will find immediate utility in prisons and law enforcement agencies around the world.

Evaluation of fentanyl immunoassay test strips for rapid in-situ detection of fentanyl and fentanyl analogs in seized samples and alternative matrices.

Ion mobility spectrometry is used for the rapid detection of drugs at points of security but are unable to differentiate some drugs leading to the instrument alarming for a drug not present in the sample. This can be particularly problematic for samples that alarm for fentanyl. In this study, fentanyl immunoassay strips were evaluated for use as a secondary test for fentanyl, including for the testing of alternative matrices, such as powders, e-liquids, and infused papers and textiles. The limit of detection of fentanyl immunoassay strips was examined along with their selectivity to 18 fentanyl analogsand 72 other drugs and cutting agents. The effectiveness of the test strips at the detection of fentanyl in the presence of other drugs was examined by testing a series of concentrations of fentanyl in solution in combination with other drugs. The testing of alternative matrices was explored with laboratory prepared samples through sampling with cotton buds and extraction in water. The fentanyl immunoassay strips detected fentanyl at concentrations of 45 ng/mL and reacted with 16 of 18 tested fentanyl analogs with carfentanil and norfentanyl being the only analogs to not react. There was no reactivity with other drugs or cutting agents. The effectiveness of the fentanyl test strips was not reduced when fentanyl was mixed with other drugs. Fentanyl was successfully detected with high sensitivity in all alternative matrices. The fentanyl immunoassay strips were found to be an effective secondary test for fentanyl and at least 16 fentanyl analogs in seized drug samples, including when mixed with other drugs. The effectiveness of the sampling methods for alternative matrices should be further evaluated using fentanyl and fentanyl analog casework samples. The use of this method by law enforcement and other agencies should be examined to assess its effectiveness and ease of use in operational settings.

Conniving for the first time of BiVO4 – rGO/CE-BN and its potential as enhanced electrochemical sensing of non-steroidal anti-androgen drug

This work focuses on the electrochemical sensing of Flutamide (FLA) drug using a ternary composite material namely reduced graphene oxide (rGO) wrapped with bismuth vanadate (BiVO4) loaded on chemically exfoliated boron nitride (CE-BN). To synthesize this material, BiVO4 was prepared using the solvothermal method; secondly, graphene oxide was prepared using the modified Hummer’s method, and CE-BN was prepared using the chemical exfoliation method. After the preparation of the individual materials, reduced graphene oxide was bound over bismuth vanadate using the wrapping technique and then loaded onto the CE-BN surface using the wet impregnation technique. After the preparation of each compound, characterization studies such as XRD, FT-IR, and FE-SEM analysis were carried out in order to confirm the structural details, formation of the compound, and other functional properties and to check the purity of the material. Finally, the confirmed compounds were used for electrochemical sensing studies in a three-electrode setup; the electrochemical performance of the BiVO4-rGO/CE-BN composite was investigated using cyclic voltammetry (CV) and digital pulse voltammetry (DPV). With lower cathodic peak potential, greater cathodic current, a better linear range (0.04–102.2 µM), a lower limit of detection (0.011 µM), and better sensitivity (3.8028 µA µM−1 cm−2) on the modified BiVO4-rGO/CE-BN, it demonstrates superior electrochemical activity towards the reduction of FLA. Furthermore, interference studies were conducted in presence of other drugs to test the selectivity of the proposed sensor, which revealed that BiVO4-rGO/CE-BN/GCE possesses a greater selectivity. In addition, the practical feasibility of the prepared sensor was tested with lake water samples, which showed a satisfactory recovery in real samples. Based on the findings, the suggested sensor (BiVO4-rGO/CE-BN/GCE) appears to be a better choice for FLA detection.

Colorimetric and fluorescent hydrazone-BODIPY probes for the detection of γ-hydroxybutyric acid (GHB) and cathinones

Consumption and abuse of drugs is a general problem, which concerns our entire society. In some cases, drugs are used for recreational purposes; but in others, they are used to commit crimes such as Drug-Facilitated Sexual Assault (DFSA). In other cases, this consumption alters the consumer mood in such a way that risky situations can rise. In any case, detection of drugs in different environment is worthwhile. Here, two new chromogenic and fluorescent probes are reported. Detection of both cathinone derivatives and γ-hydroxybutyric acid (GHB) can be carried out with naked-eye with limits of detection of 0.4 μM and 0.3 μM for GHB and 2.0 μM for ephedrone. Selectivity in the presence of other drugs has been tested. Sensing mechanisms have been studied using different spectroscopic techniques and they have been also corroborated through theoretical calculations.

Quantitative determination of clozapine in plasma using an environmentally friendly technique

A new method for the determination of clozapine in blood samples, a common antipsychotic drug, has been developed. It is based upon a dispersive liquid–liquid microextraction technique employed as the extraction method together with gas chromatography-mass spectrometry operating in selected ion monitoring (SIM). The method was fully validated including selectivity, sensitivity, accuracy, precision and recovery steps. The limit of quantification was set at 50 ng/mL. Intra and interday accuracy and precision values were lower than 17% at the concentration levels studied. Good recovery results were obtained for all concentrations. The proposed method was satisfactory applied to 10 plasma samples received at the Forensic Toxicology Service of the Forensic Science Institute of Santiago de Compostela, obtaining results within the therapeutic range. The results showed the usefulness of the analysis in any forensic toxicology laboratory and the posibility of determining clozapine in the presence of other drugs or drugs or abuse.

A A Rare Case Report of Toxic Epidermal Necrolysis with Iron Sucrose/first line Anti-tuberculosis Treatment Drugs

Toxic Epidermal Necrolysis [TEN] is life-threatening condition with mortality rate of 30-60%. Most common etiology of TEN is drug induced. Though Anaphylactic [Type I Hypersensitivity] reactions have been reported with Iron Sucrose, we present first case of TEN [Type IV Hypersensitivity], associated with Iron Sucrose along with Anti-tuberculosis treatment [ATT], to our knowledge. Iron Sucrose is considered relatively safer than other iron formulations. After 48 hours of administering Intravenous Iron Sucrose [20 mg in 200 ml N.S] infusion [first day], patient developed TEN symptoms [third day]. He was taking first line ATT drugs since past one month for Pulmonary Tuberculosis. On basis of history, 80-90% Body Surface area involvement, positive Nikolsky sign and laboratory findings, patient was diagnosed with drug induced TEN [fifth day]. For TEN management, ATT was withdrawn and patient was treated with intravenous Dexamethasone, Piperacillin/Tazobactam, Metronidazole, Pantoprazole, Intravenous fluids with dermatologically supportive local applications and patient was monitored. Patient died due to septic shock despite all resuscitative measures [seventh day]. Causality assessment (WHO UMC scale and Naranjo scale) was ‘Possible’ for both Iron Sucrose and ATT drugs. No improvement in patient’s condition after withholding ATT and short duration between Iron sucrose and symptoms of TEN onset suggests an increased likelihood of TEN induction by Iron sucrose. However, either ATT or Iron Sucrose could trigger TEN in presence of other drug. Improved understanding by physicians of these relatively unknown life-threatening ADR’s and interactions can aid in early identification and enhanced vigilance in future scenarios.&#x0D; Keywords: WHO UMC Scale, SCORTEN score, Naranjo scale, Anaphylactic reactions

Caffeine and MDMA (Ecstasy) Exacerbate ER Stress Triggered by Hyperthermia.

Drugs of abuse can cause local and systemic hyperthermia, a known trigger of endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). Another trigger of ER stress and UPR is ER calcium depletion, which causes ER exodosis, the secretion of ER-resident proteins. In rodent models, club drugs such as 3,4-methylenedioxymethamphetamine (MDMA, ‘ecstasy’) can create hyperthermic conditions in the brain and cause toxicity that is affected by the environmental temperature and the presence of other drugs, such as caffeine. In human studies, MDMA stimulated an acute, dose-dependent increase in core body temperature, but an examination of caffeine and MDMA in combination remains a topic for clinical research. Here we examine the secretion of ER-resident proteins and activation of the UPR under combined exposure to MDMA and caffeine in a cellular model of hyperthermia. We show that hyperthermia triggers the secretion of normally ER-resident proteins, and that this aberrant protein secretion is potentiated by the presence of MDMA, caffeine, or a combination of the two drugs. Hyperthermia activates the UPR but the addition of MDMA or caffeine does not alter the canonical UPR gene expression despite the drug effects on ER exodosis of UPR-related proteins. One exception was increased BiP/GRP78 mRNA levels in MDMA-treated cells exposed to hyperthermia. These findings suggest that club drug use under hyperthermic conditions exacerbates disruption of ER proteostasis, contributing to cellular toxicity.

Blood concentrations of new synthetic opioids.

Over the last decade, there has been a significant growth in the market and number of new psychoactive substances (NPS). One of the NPS groups that has grown rapidly in recent years, bringing a new set of problems, consists of new synthetic opioids. The extreme potency of these compounds poses a high risk of acute poisoning, as an overdose can cause respiratory depression. Most of the information regarding human pharmacokinetics of new opioids is based on toxicological case reports and the data on concentrations of new opioids in human blood are scarce. The interpretation of results usually requires a comparison to previously published cases; therefore, a referenced compilation of previously published concentration data would be useful. The data were collected by searching the PubMed and Scopus databases and by using the Google search engine. All the available data from articles and reports that measured new opioid concentrations in plasma, serum, or whole blood were included in the data analysis. The presented tables list the observed concentrations in fatal and nonfatal cases involving 37 novel synthetic opioids. Blood levels of new opioids are extremely difficult to interpret. Low blood concentrations of these substances do not rule out acute poisoning as their high potency creates a risk of respiratory depression even at low doses. Opioid tolerance, frequent presence of other drugs, and additional diseases make it impossible to define concentration ranges, especially the minimum fatal concentrations. This report provides quick access to the source articles quantifying novel synthetic opioids.

Competitive kinetics of adsorption onto activated carbon for emerging contaminants with contrasting physicochemical properties.

Activated carbon (AC) can be used for the removal of emerging contaminants (e.g., drugs) in water and wastewater treatment plants. In the present study, we investigated the performance of two ACs (from coconut shell and Pinnus sp.) in the adsorption of caffeine, carbamazepine, and ricobendazole considering the compounds separately and in combination in batch-scale experiments. The concentrations of the drugs were determined by a validated method using solid-phase extraction with on-line ultra-high performance liquid chromatography-tandem mass spectrometry. The most mesoporous AC provided higher drug removal. The kinetic data were described by the pseudo-second-order, Elovich, and Weber-Morris models, while the adsorption isotherms showed a better fit to the Freundlich model, indicative of multilayer adsorption. The Dubinin-Radushkevich model was used as a first approach to estimate the mean adsorption energy (E) and the results indicate that chemisorption governed the adsorption process, with E higher than 8 kJ mol-1. In the multicomponent assays, the adsorption of caffeine showed the greatest hindrance caused by the presence of other drugs. Multicomponent assays are fundamental to evaluate the potential adsorption capacity in real water treatment plants. Our study suggests that drugs with different structures and physicochemical properties may interact differently with ACs, especially in multicomponent solutions, with important implications for the design (e.g., volumes and areas of treatment plants) and operation (e.g., water residence time) of the treatment plants.