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Chemosphere Oct 2023This work aimed at investigating specific attenuation pathways of pharmaceuticals in copper- and iron-rich Mediterranean intermittent and sunlit rivers by combining lab-...
This work aimed at investigating specific attenuation pathways of pharmaceuticals in copper- and iron-rich Mediterranean intermittent and sunlit rivers by combining lab- and field-scale studies. Poorly photodegradable and biodegradable compounds such as fluconazole, oxazepam and venlafaxine attenuated in two river stretches with short hydraulic residence times (<3 h). This result was assumed to be related to their capacity to interact with photoreactive free Cu and Fe or their associated oxides. Lab-scale photodegradation experiments under simulated solar irradiation revealed the beneficial impact of a mixture Cu and colloidal iron hydroxides at environmental concentrations and at neutral pH on the pharmaceuticals photodegradation kinetic rate constants. These latter were consistent with the in-stream attenuation rate constants of targeted contaminants which ranged from 0.104 to 0.154 h. Further identification of phototransformation products by LC-HRMS highlighted reductive transformation pathways including reductive dehalogenation and hydrogenation reactions. Several TPs were found to be stable under irradiation and were detected in field monitoring, accordingly. This was ascribed to the formation of a Cu/Fe composite material under solar irradiation with photocatalytic properties. The role of Cu was to trap the electron in the conduction band of the iron-based photocatalyst, which promoted separation efficiency of electron-hole pairs as well as enhanced photoreduction processes at the expense of oxidation ones. Even though, these mechanisms have been reported in water treatment field for organic micropollutants removal, their significance was demonstrated for the first time in natural settings.
Topics: Iron; Copper; Rivers; Water Pollutants, Chemical; Oxidation-Reduction; Pharmaceutical Preparations
PubMed: 37557999
DOI: 10.1016/j.chemosphere.2023.139762 -
Forensic Chemistry (Amsterdam,... Sep 2023An LC-MS/MS method for the analysis of 53 benzodiazepines, including various designer benzodiazepines, was developed. The developed method was applied to a total of 79...
An LC-MS/MS method for the analysis of 53 benzodiazepines, including various designer benzodiazepines, was developed. The developed method was applied to a total of 79 illicit street drug samples collected in Chicago, IL. Of these samples, 68 (84%) had detectable amounts of at least one benzodiazepine. Further, of the 53 benzodiazepines included in the developed method just 14 were measured in samples. Clonazolam, a potent designer benzodiazepine and derivative of clonazepam, was the most frequently measured benzodiazepine in 63% of samples and was measured in the highest concentrations. Other benzodiazepines measured in more than 10% of samples included clonazepam, alprazolam, flualprazolam, and oxazepam. Mixtures of benzodiazepines were frequently measured in samples, with just 24% of samples containing just one benzodiazepine. To determine the response of benzodiazepines on a rapid, point-of-use drug checking tool, all 53 benzodiazepine standards were screened on a lateral flow immunoassay benzodiazepine test strip. Sixty eight percent of standards gave a positive BTS response at a concentration of 20 μg/mL, demonstrating BTS have response to a wide variety of benzodiazepines, including many designer benzodiazepines. A comparison of this data to previous data reported for the same samples demonstrated all samples containing a benzodiazepine also had an opioid present, with fentanyl being present in 94% of benzodiazepine samples. These results highlight high rates of polysubstance drug presence in Chicago, IL illicit drug samples, posing an increased risk of drug overdoses in people who use drugs.
PubMed: 37483533
DOI: 10.1016/j.forc.2023.100512 -
Forensic Science International Dec 2023The primary objective of postmortem forensic toxicology is to determine if toxicological substances detected in bodily material of victims have contributed to the death...
INTRODUCTION
The primary objective of postmortem forensic toxicology is to determine if toxicological substances detected in bodily material of victims have contributed to the death of the victim. Interpretation of postmortem drug concentrations is hindered by the fact that time and site dependent variations in postmortem drug concentrations occur, as a result of postmortem redistribution (PMR). An often-used marker for the occurrence of PMR, is the cardiac blood concentration/peripheral blood concentration ratio (C/P ratio) of a drug. In this study, we investigated the relationship between 13 variables and the C/P ratios of amphetamines and benzodiazepines.
METHOD
Toxicological results of all postmortem cases that were positive for amphetamines (amphetamine, MDMA, MDA) and/or benzodiazepines (diazepam, desmethyldiazepam, temazepam, oxazepam, midazolam, α-hydroxymidazolam) investigated by the Netherlands Forensic Institute between January 1 2010 and July 31 2020 were reviewed. A total of 112 amphetamine positive cases (224 paired specimen) and 179 benzodiazepine positive cases (358 paired specimen) were selected. The C/P ratios were determined for all selected cases. Ratios were compared between subgroups by performing either a Mann-Whitney U test or a Kruskal-Wallis test followed by post-hoc Mann-Whitney U test.
RESULTS
After dividing cases in quartiles based on their amphetamine concentration in femoral blood, the amphetamine C/P ratio was significantly lower in cases with a high amphetamine concentration (quartile 4) compared to cases with a low amphetamine concentration (quartiles 1 and 2) with median C/P ratios of 1.6, 2.4 and 2.2, respectively (p-value<0.001 and p-value=0.001, respectively). The MDA C/P ratio was significantly higher in cases where trauma was the cause of death compared to cases where intoxication was the cause of death with median C/P ratios of 3.3 and 1.6, respectively (p-value<0.001). The MDA C/P ratio was also significantly lower in cases where resuscitation was attempted compared to cases where no resuscitation was attempted with median C/P ratios of 1.6 and 2.4, respectively (p-value=0.003). However, a significant dependency between the variables cause of death and attempted resuscitation was observed. No significant differences in benzodiazepine C/P ratios were observed between subgroups of any of the investigated variables. However, the low p-value of BMI suggests a potential difference in midazolam C/P ratio between BMI subgroups (p-value=0.027).
CONCLUSION
When interpreting postmortem toxicological results, it might prove useful to take the above-mentioned variables into account.
Topics: Humans; Benzodiazepines; Midazolam; Postmortem Changes; Autopsy; Amphetamine
PubMed: 37931468
DOI: 10.1016/j.forsciint.2023.111876 -
Frontiers in Psychiatry 2023The prevalence of patent foramen ovale (PFO) is 15-35% among adults. The role of right-to-left shunting through the PFO, anxiety, depression, and hypoxemia in the...
The prevalence of patent foramen ovale (PFO) is 15-35% among adults. The role of right-to-left shunting through the PFO, anxiety, depression, and hypoxemia in the systemic circulation remains poorly understood. Herein, we present the case of a 52-year-old woman with no heart or lung disease, who was admitted due to anxiety for 5 months and had symptom exacerbation with dizziness for 4 days and presented with cyanosis. She was noted to have acute hypoxemia, with an oxygen saturation of 94.48% on room air, and arterial blood gas showed an oxygen tension of 65.64 mmHg. Agitated saline contrast echocardiography showed right-to-left shunting due to PFO. Arteriovenous fistula, pneumonia, pulmonary embolism, pulmonary hypertension, congestion peripheral cyanosis, ischemic peripheral cyanosis, and methemoglobin were excluded. Additionally, the patient improved by taking Paroxetine, Oxazepam, and Olanzapine. Her oxygen tension returned to 90.42 mmHg, and her symptoms resolved. In the case of severe anxiety and depression, right-to-left shunting through the PFO may cause acute systemic hypoxemia a flow-driven mechanism, occasionally manifesting as cyanosis. When anxiety improved, hypoxia also improved. Thus, the treatment of anxiety and depression seems effective in improving hypoxemia. Notably, this is a rare report, and we hope to draw the attention of psychosomatic specialists, psychiatrists, and clinicians to seek the relationship between anxiety appearing as acute stress and PFO. This may be a new therapeutic method for treating severe anxiety disorder.
PubMed: 37674554
DOI: 10.3389/fpsyt.2023.1229995 -
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 -
Journal of Pharmaceutical and... Mar 2024Phase II metabolites play an important role in diazepam-related cases. The study aimed to assess the stability of diazepam's phase II metabolites in dried blood spots on...
UNLABELLED
Phase II metabolites play an important role in diazepam-related cases. The study aimed to assess the stability of diazepam's phase II metabolites in dried blood spots on filter paper.
METHODS
A piece of filter paper was spotted with 100 µL of whole blood (added 1% sodium fluoride as needed) obtained from participant who received 5 mg diazepam orally, air dried for 2 h at room temperature, and then stored at different conditions. Whole spots were cut at 0.1 cm from the outer edge of blood spots at post-consumption time-points of prior (zero), 5, 16, 35, 61, 120 days and 1, 1.5 years. Analytes were extracted with methanol/water mixture (8:2, v/v) and determined using HPLC-MS/MS. Decomposition rules were analyzed by a statistical software "SPSS".
RESULTS
Temazepam glucuronide remained stable (0.5-18.6% loss) at 20 ℃ and at 20 ℃ with 1% sodium fluoride for 16 days, while it was unstable after 5 days at 4 ℃ (21.1-26.2% loss) and - 20 ℃ (28.9 - 34.4% loss). After 35 days, temazepam glucuronide concentrations began to fluctuate significantly under all conditions, and an obvious increase (290.4-355.1%) was observed in 1.5 years. Oxazepam glucuronide was always unstable after 5 days, the percentage loss was even 100% when it was stored for 61 days and 1.5 years.
CONCLUSIONS
Dried blood spots on ordinary filter paper are recommended to be stored at 20 ℃ or 20 ℃ with 1% sodium fluoride within 16 days. Samples should be analyzed immediately or stored in sterile and dry media.
Topics: Humans; Tandem Mass Spectrometry; S Phase; Sodium Fluoride; Diazepam; Filtration
PubMed: 38157738
DOI: 10.1016/j.jpba.2023.115921 -
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 -
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