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Environmental Science and Pollution... May 2024Groundwater contamination by pharmaceutically active compounds (PhACs) has been considered a public health concern worldwide. Alongside the potential toxicological risk... (Review)
Review
Groundwater contamination by pharmaceutically active compounds (PhACs) has been considered a public health concern worldwide. Alongside the potential toxicological risk of these organic substances, many countries still rely on groundwater for drinking water supply. Thus, this study identified a priority list of seven licit PhACs, comprising acetaminophen (ACT), tramadol (TRA), carbamazepine (CBZ), erythromycin (ERY), sulfamethoxazole (SMX), metformin (MET), and oxazepam (OXZ). Consumption, concentration, and human toxicity in silico results were collected from open access databases. These three indicators were analyzed separately and grouped through a general risk index. The consumption index (data from the USA and Brazil) indicated that ACT, TRA, and MET are the most consumed. Monitoring samples from the USA and Europe (n = 816) indicated that OXZ and ERY stand out as the higher occurrence index considering both regions, but the ranking for each region showed considerable differences. When assessing toxicological risk, an index ≥ 0.5 was attributed to CBZ, MET, OXZ, SMX, and TRA. The general risk indicated the need to be attentive to MET, OXZ, and TRA as they presented ≥ 0.5 index values for at least two indicators.
Topics: Groundwater; Humans; Water Pollutants, Chemical; Pharmaceutical Preparations; Environmental Monitoring; Carbamazepine; Drinking Water; Brazil
PubMed: 38691293
DOI: 10.1007/s11356-024-33423-6 -
The Science of the Total Environment Sep 2023The presence of pharmaceuticals (PHA) and narcotics (NAR) in wastewater (WW) has attracting growing interest due to concern for aquatic environment and the possibility...
Pharmaceutical and narcotics monitoring in Brno wastewater system and estimation of seasonal effect on the abuse of illicit drugs by a wastewater-based epidemiology approach.
The presence of pharmaceuticals (PHA) and narcotics (NAR) in wastewater (WW) has attracting growing interest due to concern for aquatic environment and the possibility to exploit their presence to estimate drug consumption by population. This work aims to (i) quantify PHA and NAR in the WW of the Brno metropolitan area, (ii) determine the effectiveness of the current conventional wastewater treatment plant (WWTP), and (iii) estimate the illicit drug (ID) consumption. 23 PHA and 9 NAR were frequently detected in the untreated WW and studied for their removal. One year monitoring was carried out to highlight a possible seasonal pattern with PHA and NAR load in WW, WWTP effectiveness, and illicit consumption. Results highlighted that the most abundant PHA and NAR were caffeine (73.9 ± 6.9 μg L) and methamphetamine (2.3 ± 0.1 μg L) while oxazepam (0.13 ± 0.05 μg L) and EDDP (0.02 ± 0.01 μg L) were the lowest ones, respectively. Only paracetamol, caffeine, atenolol, ciprofloxacin, amphetamine, cocaine, morphine, and benzoylecgonine exhibited a high biodegradability being removed almost completely (> 90 %). A predominant illicit use of methamphetamine was estimated (17 ± 0.6 doses 1000.inh d) that might suggest a higher number of consumers than previous official estimation. A lower abuse of cocaine (2.7 ± 0.5 doses 1000.inh d), amphetamine (2.2 ± 0.3 doses 1000.inh d), methadone (1.1 ± 0.2 doses 1000.inh d), heroin (0.9 ± 0.2 doses 1000.inh d), and MDMA (0.7 ± 0.1 doses 1000.inh d) was found. A seasonality pattern was highlighted for some PHA and NAR influent load and removal, and, about ID consumption, only for heroin and methadone. These results will be useful for water utilities, to enhance the knowledge about the presence and removal of PHA and NAR, and local and national authorities to evaluate and counteract the problem of ID abuse.
Topics: Humans; Wastewater; Illicit Drugs; Narcotics; Wastewater-Based Epidemiological Monitoring; Heroin; Seasons; Caffeine; Water Pollutants, Chemical; Environmental Monitoring; Amphetamine; Methamphetamine; Cocaine; Methadone; Substance Abuse Detection; Substance-Related Disorders
PubMed: 37263433
DOI: 10.1016/j.scitotenv.2023.164386 -
Cureus Mar 2024Anesthesiologists often use benzodiazepines (BZDs) due to their remarkable amnestic and anxiolytic capabilities. Because of this, they are perfect for use during the... (Review)
Review
Anesthesiologists often use benzodiazepines (BZDs) due to their remarkable amnestic and anxiolytic capabilities. Because of this, they are perfect for use during the perioperative phase, when patients' anxiety levels are already high. Remimazolam has replaced certain commonly used intravenous (IV) anesthetics due to its excellent safety profile, rapid onset of action, and short half-life. The four classes of BZDs, 2-keto-benzodiazepines, 3-hydroxy-benzodiazepines, triazolobenzodiazepines, and 7-nitro-benzodiazepines based on chemical structure, provide various levels of drowsiness, forgetfulness, and anxiolysis. Based on their elimination half-life, short-acting BZDs typically have a half-life ranging from one to 12 hours, e.g., oxazepam; intermediate-acting BZDs have an average elimination half-life of 12 to 40 hours, e.g., alprazolam; and long-acting BZDs have an average elimination half-life of more than 40 hours, e.g., diazepam. The chloride ion channel is conformationally shifted by the benzodiazepine molecule resulting in central nervous system (CNS) inhibition and hyperpolarization. Each type of benzodiazepine has a favored use. For example, diazepam is used to treat anxiety. Midazolam is used for its anxiolytic and anterograde amnestic effects during the perioperative phase. Anxiety and epilepsy are two conditions that lorazepam effectively treats. There are now phase II and III clinical studies investigating remimazolam. It is not sensitive to alterations in its surroundings and has a brief half-life so that it may be removed rapidly, even after extensive infusion. Being a soft drug means the body easily breaks it down via metabolism, which explains many features. Remimazolam is hydrolyzed into methanol and its carboxylic acid metabolite CNS 7054 by esterase metabolism. Therefore, remimazolam has a shorter onset time and faster recovery than other BZDs. Remimazolam is metabolized independently of any particular organ. Patients with hepatic and renal problems will not see any changes in metabolism or excretion since the drug's ester moiety makes it a substrate for general tissue esterase enzymes. Like its predecessor, midazolam, it has a high potential for addiction. Some side effects that could occur during infusion include headaches and drowsiness. In clinical trials, hypotension, respiratory depression, and bradycardia were noted in participants. BZDs are helpful when used in conjunction with anesthesia. Remimazolam stands out, thanks to its unique pharmacokinetics, pharmacodynamics, safety profile, and potential medical applications. Its desirable properties make it a potential surgical premedication and sedative in the critical care unit. Anesthesiologists and other doctors could have access to more consistent and safer medication. However, additional comprehensive clinical trials are necessary to understand remimazolam's advantages and disadvantages.
PubMed: 38686236
DOI: 10.7759/cureus.57260 -
Journal of Analytical Toxicology Jul 2023Postmortem whole blood samples can differ greatly in quality where hyperlipemia is a frequent variable that can influence the results of analytical methods. The aim of...
Postmortem whole blood samples can differ greatly in quality where hyperlipemia is a frequent variable that can influence the results of analytical methods. The aim of this study was to investigate the influence of lipemia on postmortem analysis as well as demonstrate the usage of Intralipid in comparison to pooled postmortem lipids as matrix additives for meaningful evaluation and validation of hyperlipidemic postmortem samples. Hyperlipidemic blood samples were simulated by adding different concentrations of Intralipid or pooled authentic postmortem lipids to bovine whole blood. The hyperlipidemic blood samples were spiked with 14 benzodiazepines and five sedative and antianxiety drugs (alprazolam, clonazepam, 7-aminoclonazepam, diazepam, flunitrazepam, 7-aminoflunitrazepam, hydroxyzine, lorazepam, midazolam, nitrazepam, 7-aminonitrazepam, nordazepam, oxazepam, propiomazine, dihydropropiomazine, temazepam, triazolam, zolpidem and zopiclone). Samples were prepared with liquid-liquid extraction followed by ultra-high performance liquid chromatography-mass spectrometry. The effects of lipemia on the recovery of analytes and internal standards (ISs) were evaluated to determine the effect of, and any differences between, the two additives. Lipemia was found to cause major interference when quantifying the analytes. For most analytes, the ISs could compensate for analyte losses. However, the most hydrophilic analytes (7-amino metabolites), together with the most lipophilic analytes (propiomazine and dihydropropiomazine), were greatly affected by lipemia (<50% recovery), and the IS could not compensate for analyte losses. In general, lower analyte recoveries were observed for samples with Intralipid as a lipemic additive in comparison to those containing pooled postmortem lipids. Both Intralipid and pooled postmortem lipids showed marked effects on the analytical results. Intralipid gave a good indication of the effects of lipemia and could be a useful tool for making a meaningful evaluation of hyperlipidemic postmortem samples during the method development and validation.
Topics: Animals; Cattle; Tandem Mass Spectrometry; Benzodiazepines; Phospholipids; Hyperlipidemias
PubMed: 37130054
DOI: 10.1093/jat/bkad025 -
Ecotoxicology and Environmental Safety Jul 2023Pharmaceutically active compounds are common and increasing in the aquatic environment. Evidence suggests they have adverse effects on non-target organisms, and they are...
Pharmaceutically active compounds are common and increasing in the aquatic environment. Evidence suggests they have adverse effects on non-target organisms, and they are classified as emerging pollutants for a variety of aquatic organisms. To determine the effects of environmentally relevant levels of psychoactive compounds on non-target organisms, we analyzed cardiac and locomotory activity in early developmental stages of marbled crayfish Procambarus virginalis. Responses to sertraline, methamphetamine, and a mixture of citalopram, oxazepam, sertraline, tramadol, venlafaxine, and methamphetamine at a concentration of 1 µg L of each compound were assessed. On day four of exposure, cardiac activity was recorded for 5 min, and on day eight, locomotory activity was recorded for 15 min. There was a significant increase (p < 0.01) in heart rate in methamphetamine-exposed and Mix-exposed juveniles compared to the unexposed control and there was significant difference (p < 0.01) in proportion of time (activity %) was observed with sertraline-exposed, whereas velocity, and distance moved did not significantly differ (p > 0.05) in exposed and control animals. These findings revealed that low concentrations of chemicals and their mixtures can modify the physiological state of aquatic animals without outward manifestations (activity, distance moved, and velocity). Aquatic animals can be impacted earlier than is visible, but effects can potentially lead to substantial changes in populations and in ecosystem processes. Additional research to investigate chemical combinations, exposure systems, and organism physiological and molecular responses may provide evidence of broad impact of environmental pharmaceuticals.
Topics: Animals; Astacoidea; Ecosystem; Sertraline; Methamphetamine; Locomotion; Water Pollutants, Chemical
PubMed: 37267780
DOI: 10.1016/j.ecoenv.2023.115084 -
Talanta Aug 2023Benzodiazepines can make victims more docile, they are frequently used in drug-facilitated crimes, such as robberies and sexual assaults. Therefore, it is essential to...
Benzodiazepines can make victims more docile, they are frequently used in drug-facilitated crimes, such as robberies and sexual assaults. Therefore, it is essential to develop techniques for determining whether these chemicals are present in relation with illegal activity is crucial. Therefore, to determine the presence of five benzodiazepines (alprazolam, clonazepam, diazepam, lorazepam, and oxazepam) in water, alcoholic beverages, and non-alcoholic beverages, a simple and direct, miniaturized, and effective vortex assisted ultrasound based microextraction using solidification of floating organic droplets (VAUS-ME-SFO) in combination with LC-MS/MS was developed. 1-Undecanol and acetonitrile, respectively, served as the extractant and disperser solvents. Many other parameters affect the efficiency of the developed analytical procedure VAUS-ME-SFO/LC-MS/MS. These parameters were optimized using Plackett Burman Design and Central Composite Design to obtain reliable results. The optimum conditions for the extraction were: 10.0 mL of sample; 180 μL acetonitrile, as a dispersive solvent; 200 μL of 1-undecanol, as an extraction solvent; pH 7; 105 s of vortex agitation; 120 s of ultrasonication application and 3 min of centrifugation at 7000 rpm. The benzodiazepines were separated by a chromatographic separation technique carried out by a UPLC system consisting of a binary mobile phase. The solvent system comprises of 0.1% Formic acid in Milli-Q (Solvent A) and 0.1% Formic acid in ACN (Solvent B) with a gradient flow of 3.5 min total analysis time. Under the optimized conditions, the calibration curve was studied in the range of 0.124-7.810 ng mL. The regression correlation coefficient (R) value of all targeted analytes ranges from 0.993 to 0.999. The LOD and LOQ of VAUS-ME-SFO methods using LC-MS/MS analysis range from 0.316 to 0.968 ng mL and 1.055-3.277 ng mL respectively. The repeatability within a day varied from 0.6 to 3.5%, and the reproducibility across days varied from 2.2 to 6.3%. The recoveries ranges for water, alcoholic and non-alcoholic beverages from 70.77 to 114.53%, 63.20-102.21% and 66.23-113.28% respectively. Further, the degradation kinetics was studied to establish the half-life of each targeted analyte in the matrix undertaken in the study. The water samples were classified based on their BDZs residues. This implies that the more health care and anthropogenic activity, the more the BDZs residue will be in water samples.
Topics: Benzodiazepines; Chromatography, Liquid; Water; Reproducibility of Results; Tandem Mass Spectrometry; Solvents; Beverages; Liquid Phase Microextraction
PubMed: 37121139
DOI: 10.1016/j.talanta.2023.124572 -
Journal of Chromatography. B,... Jan 2024A new efficient ZnO-AlO nanocomposite (ZANC) was synthesized to form solid-phase microextraction (SPME) fiber. The prepared fiber was used for trace determination of...
A new efficient ZnO-AlO nanocomposite (ZANC) was synthesized to form solid-phase microextraction (SPME) fiber. The prepared fiber was used for trace determination of benzodiazepines by gas chromatography-flame ionization detector in urine samples. The effective parameters on the extraction process including extraction time, salt percentage, desorption time and sample pH were optimized by a factorial design method. The method was evaluated at the optimum conditions and limits of detection (LODs) were calculated 20 µg/L for diazepam and oxazepam. The method repeatability for oxazepam and diazepam (50 µg/L, n = 4) was calculated at 8.8 % and 6.4 %. Also, the method reproducibility was obtained, 7.45 % and 6.61 % for oxazepam and diazepam (50 µg/L, n = 4). Also, fiber-to-fiber relative standard deviation (RSDs%) for the target analytes were less than 15.5 %. The method linearity is within the range of 62-500 µg/L for diazepam and oxazepam. The ZANC-SPME fiber showed a good lifetime (60 times) with high chemical stability. The high thermal stability of ZANC-SPME fiber was attained at 280 °C. The extraction results of poly dimethylsiloxan/divinyl benzene (PDMS/DVB) fiber were compared by ZANC-SPME fiber. Therefore, the method is proposed as a suitable technique for benzodiazepines detection in the urine sample.
Topics: Diazepam; Oxazepam; Solid Phase Microextraction; Zinc Oxide; Reproducibility of Results; Benzodiazepines; Nanocomposites
PubMed: 38104432
DOI: 10.1016/j.jchromb.2023.123966 -
The Science of the Total Environment Jun 2024Untangling the consumption rates of psychiatric drugs and their metabolites/ transformation products-(TPs) through wastewater gains attention lately. However, the...
Unravelling psychoactive substances and their metabolites and transformation products: High-Resolution Mass Spectrometry approaches for comprehensive target and suspect screening in wastewater.
Untangling the consumption rates of psychiatric drugs and their metabolites/ transformation products-(TPs) through wastewater gains attention lately. However, the potential environmental impact caused by their release remains ambiguous. As it follows, the monitoring of this class of pharmaceuticals as well as the evaluation of their potential toxicity is a matter of high concern. In the light of the above, here, wastewater samples, were collected in a 1-year and a half sampling campaign (2020-2021) and were further subjected to solid phase extraction. A Q Exactive Focus Orbitrap mass analyzer was employed for the analysis of the samples. For the data curation, except of the monitoring of targets, a comprehensive suspect screening workflow was developed and slightly optimized based on a lab made HRMS database for the investigation of legally or illegally prescribed psychiatric drugs and their relevant metabolites/TPs in influents and effluents. Carbamazepine and amisulpride were quantified at the highest mean concentrations 243 and 225 ng/L respectively, in influents. In effluents, the highest mean concentrations were calculated for carbamazepine (180 ng/L) and venlafaxine (117 ng/L). The implementation of suspect screening approach enhanced the comprehensiveness of analysis by detecting 29 compounds not included in the target list. O-Desmethylvenlafaxine was the predominant metabolite in influents presenting a mean concentration equal to 87 ng/L while the same pattern was also noticed in effluents where the mean concentration was up to 91 ng/L. From the group of suspect compounds for which no analytical standards were available, the predominant compounds with detection frequency 100 % were norephedrine and codeine in influents while in effluents, oxazepam was detected in 81 % of the analyzed samples. Finally, in silico and mathematical tools were employed for the assessment of the risk posed to environmental systems. Most of the detected compounds present high risk in all trophic levels.
Topics: Wastewater; Water Pollutants, Chemical; Psychotropic Drugs; Environmental Monitoring; Mass Spectrometry; Solid Phase Extraction
PubMed: 38688363
DOI: 10.1016/j.scitotenv.2024.172867 -
Therapeutic Drug Monitoring Mar 2024Legally prescribed benzodiazepines (BZDs) and designer BZDs are widely misused and must be determined in multiple contexts (eg, overdose, drug-facilitated sexual...
BACKGROUND
Legally prescribed benzodiazepines (BZDs) and designer BZDs are widely misused and must be determined in multiple contexts (eg, overdose, drug-facilitated sexual assaults, or driving under the influence of drugs). This study aimed to develop a method for measuring serum BZD levels using probe electrospray ionization (PESI) mass spectrometry and an isotope dilution approach.
METHODS
A tandem mass spectrometer equipped with a probe electrospray ionization source in multiple reaction monitoring mode was used. Isotope dilution was applied for quantification using a deuterated internal standard at a fixed concentration for alprazolam, bromazepam, diazepam, nordiazepam, oxazepam, temazepam, zolpidem, and zopiclone. This method included designer BZDs: clonazolam, deschloroetizolam, diclazepam, etizolam, flualprazolam, flubromazepam, flubromazolam, meclonazepam, nifoxipam, and pyrazolam. Sample preparation was done by mixing 10 µL of serum with 500 µL of an ethanol/ammonium formate 0.01 mol/L buffer. Complete validation was performed, and the method was compared with liquid chromatography coupled with mass spectrometry (LC-MS/MS) and immunoassays (IC) by analyzing 40 real samples.
RESULTS
The analysis time for identification and quantification of the 18 molecules was 2.5 minutes. This method was fully validated, and the limits of quantification varied from 5 to 50 mcg/L depending on the molecule. In the 40 real samples, 100% of molecules (n = 89) were detected by both LC-MS/MS and PESI-MS/MS, and regression analysis showed excellent agreement between the 2 methods (r2 = 0.98). On IC, bromazepam and zolpidem were not detected in 2 and 1 cases, respectively.
CONCLUSIONS
PESI-MS/MS allows serum BZD detection and measurement. Given the isotope dilution approach, a calibration curve was not required, and its performance was similar to that of LC-MS/MS, and its specificity was higher than that of IC.
PubMed: 38498915
DOI: 10.1097/FTD.0000000000001189 -
Drug Testing and Analysis Jan 2024Analysis of hair collected from putrefied or skeletal bodies is always complex and must take into account several pitfalls, such as external contamination and...
Analysis of hair collected from putrefied or skeletal bodies is always complex and must take into account several pitfalls, such as external contamination and contamination by biological fluids. This work presents a case of particular complexity. A skeletonized body was discovered on a country road. A tuft of brown hair, detached from the scalp, irregular in length, non-oriented, in contact with soil and vegetation, was removed. An anthropological examination was carried out and genetic samples were taken from the right femoral shaft. After about 10 washes with warm water and dichloromethane, the tuft of hair was analyzed without segmentation. General unknown screening was performed by liquid chromatography system coupled to a high-resolution mass spectrometry (LC-HRMS) after incubation in pH 9.5 borate buffer and liquid-liquid extraction. Specific Multiple Reaction Monitoring (MRM) methods for date rape drugs were carried out by liquid chromatography system coupled to a tandem mass spectrometry (LC-MS/MS). The anthropological examination allowed to determine that the victim was a female individual, over 60 years old, the death dating from 3 months to 1 year. Comparison of the DNA results with the Missing Persons Index led to the identification, a 60-year-old woman who disappeared 5 months earlier. Hair analysis showed the presence of oxazepam (361 pg/mg), nordiazepam (54 pg/mg), and alimemazine (5 pg/mg). The interpretation of these concentrations is extremely difficult due to the risk of degradation of the hair cuticle during prolonged stay in the soil, as well as of contamination by putrefactive fluids. The authors discuss the value of using multiple biological and non-biological matrices in this context to improve the interpretation of the results.
PubMed: 38243699
DOI: 10.1002/dta.3649