-
Nanomaterials (Basel, Switzerland) May 2024Contamination by pharmaceuticals adversely affects the quality of natural water, causing environmental and health concerns. In this study, target drugs (oxazepam, OZ,...
Contamination by pharmaceuticals adversely affects the quality of natural water, causing environmental and health concerns. In this study, target drugs (oxazepam, OZ, 17-α-ethinylestradiol, EE2, and drospirenone, DRO), which have been extensively detected in the effluents of WWTPs over the past decades, were selected. We report here a new photoactive system, operating under visible light, capable of degrading EE2, OZ and DRO in water. The photocatalytic system comprised glass spheres coated with nanostructured, solvothermally treated WO that improves the ease of handling of the photocatalyst and allows for the implementation of a continuous flow process. The photocatalytic system based on solvothermal WO shows much better results in terms of photocurrent generation and photocatalyst stability with respect to state-of-the-art WO nanoparticles. Results herein obtained demonstrate that the proposed flow system is a promising prototype for enhanced contaminant degradation exploiting advanced oxidation processes.
PubMed: 38786816
DOI: 10.3390/nano14100860 -
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 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 -
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 -
Nature Communications Apr 2024Between 30% and 70% of patients with breast cancer have pre-existing chronic conditions, and more than half are on long-term non-cancer medication at the time of...
Between 30% and 70% of patients with breast cancer have pre-existing chronic conditions, and more than half are on long-term non-cancer medication at the time of diagnosis. Preliminary epidemiological evidence suggests that some non-cancer medications may affect breast cancer risk, recurrence, and survival. In this nationwide cohort study, we assessed the association between medication use at breast cancer diagnosis and survival. We included 235,368 French women with newly diagnosed non-metastatic breast cancer. In analyzes of 288 medications, we identified eight medications positively associated with either overall survival or disease-free survival: rabeprazole, alverine, atenolol, simvastatin, rosuvastatin, estriol (vaginal or transmucosal), nomegestrol, and hypromellose; and eight medications negatively associated with overall survival or disease-free survival: ferrous fumarate, prednisolone, carbimazole, pristinamycin, oxazepam, alprazolam, hydroxyzine, and mianserin. Full results are available online from an interactive platform ( https://adrenaline.curie.fr ). This resource provides hypotheses for drugs that may naturally influence breast cancer evolution.
Topics: Humans; Female; Breast Neoplasms; Cohort Studies; Comorbidity; Simvastatin
PubMed: 38580683
DOI: 10.1038/s41467-024-47002-3 -
Forensic Toxicology Apr 2024Toxicological analyses of biological samples play important roles in forensic and clinical investigations. Ingested drugs are excreted in urine as conjugates with...
PURPOSE
Toxicological analyses of biological samples play important roles in forensic and clinical investigations. Ingested drugs are excreted in urine as conjugates with endogenous substances such as glucuronic acid; hydrolyzing these conjugates improves the determination of target drugs by liquid chromatography-tandem mass spectrometry (LC-MS/MS). In this study, we sought to improve the enzymatic hydrolysis of glucuronide conjugates of five psychoactive drugs (11-nor-9-carboxy-Δ-tetrahydrocannabinol, oxazepam, lorazepam, temazepam, and amitriptyline).
METHODS
The efficiency of enzymatic hydrolysis of glucuronide conjugates in urine was optimized by varying temperature, enzyme volume, and reaction time. The hydrolysis was performed directly on extraction columns. This analysis method using LC-MS/MS was applied to forensic autopsy samples after thorough validation.
RESULTS
We found that the recombinant β-glucuronidase B-One® quantitatively hydrolyzed these conjugates within 3 min at room temperature directly on extraction columns. This on-column method saved time and eliminated the loss of valuable samples during transfer to the extraction column. LC-MS/MS-based calibration curves processed with this method showed good linearity, with r values exceeding 0.998. The intra- and inter-day accuracies and precisions of the method were 93.0-109.7% and 0.8-8.8%, respectively. The recovery efficiencies were in the range of 56.1-104.5%. Matrix effects were between 78.9 and 126.9%.
CONCLUSIONS
We have established an LC-MS/MS method for five psychoactive drugs in urine after enzymatic hydrolysis of glucuronide conjugates directly on extraction columns. The method was successfully applied to forensic autopsy samples. The established method will have broad applications, including forensic and clinical toxicological investigations.
PubMed: 38557936
DOI: 10.1007/s11419-024-00685-1 -
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 -
Polymers Feb 2024In this research, a molecularly imprinted polymer (MIP) was synthesized by precipitation polymerization using oxazepam (OZ) as a template molecule and was subsequently...
In this research, a molecularly imprinted polymer (MIP) was synthesized by precipitation polymerization using oxazepam (OZ) as a template molecule and was subsequently applied as a selective sorbent for the extraction of diazepam (DZP) and its metabolites in urine samples using an SPE cartridge. OZ, temazepam (TZ), nordiazepam (NZ) and DZP were analyzed in the final extracts by high-performance liquid chromatography with diode array detection (HPLC-DAD). The SPE extraction steps were optimized, and the evaluation of an imprinting factor was carried out. The selectivity of the method for OZ versus structurally related benzodiazepines (BZDs), such as bromazepam (BRZ), tetrazepam (TTZ) and halazepam (HZ), was investigated. Under the optimum conditions, the proposed methodology provided good linearity in the range of 10-1500 ng/mL, with limit of detection values between 13.5 and 21.1 ng/mL and recovery levels for DZP and its metabolites from 89.0 to 93.9% (RSD ≤ 8%) at a concentration level of 1000 ng/mL. The proposed method exhibited good selectivity, precision and accuracy and was applied to the analysis of urine samples from a real case of DZP intake.
PubMed: 38475318
DOI: 10.3390/polym16050635 -
Pharmaceutics Feb 2024Benzodiazepines (BZDs) such as oxazepam are commonly prescribed depressant drugs known for their anxiolytic, hypnotic, muscle relaxant, and anticonvulsant effects and...
Benzodiazepines (BZDs) such as oxazepam are commonly prescribed depressant drugs known for their anxiolytic, hypnotic, muscle relaxant, and anticonvulsant effects and are frequently used in conjunction with other illicit drugs including cannabis. Oxazepam is metabolized in an enantiomeric-specific manner by glucuronidation, with S-oxazepam metabolized primarily by UGT2B15 and R-oxazepam glucuronidation mediated by both UGT 1A9 and 2B7. The goal of the present study was to evaluate the potential inhibitory effects of major cannabinoids, Δ-tetrahydrocannabinol (THC) and cannabidiol (CBD), and major THC metabolites, 11-hydroxy-Δ-tetrahydrocannabinol (11-OH-THC) and 11-nor-9-carboxy-Δ-tetrahydrocannabinol (11-COOH-THC), on the UGT-mediated metabolism of R- and S-oxazepam. The cannabinoids and metabolites were screened as inhibitors of R- and S-oxazepam glucuronidation in microsomes isolated from HEK293 cells overexpressing individual UGT enzymes (rUGTs). The IC values were determined in human liver microsomes (HLM), human kidney microsomes (HKM), and rUGTs and utilized to estimate the nonspecific, binding-corrected K (K) values and predict the area under the concentration-time curve ratio (AUCR). The estimated K values observed in HLM for S- and R-oxazepam glucuronidation by CBD, 11-OH-THC, and THC were in the micromolar range (0.82 to 3.7 µM), with the K values observed for R-oxazepam glucuronidation approximately 2- to 5-fold lower as compared to those observed for S-oxazepam glucuronidation. The mechanistic static modeling predicted a potential clinically significant interaction between oral THC and CBD with oxazepam, with the AUCR values ranging from 1.25 to 3.45. These data suggest a pharmacokinetic drug-drug interaction when major cannabinoids like CBD or THC and oxazepam are concurrently administered.
PubMed: 38399297
DOI: 10.3390/pharmaceutics16020243 -
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