-
Water Research May 2024The use of treated wastewater (TWW) for agricultural irrigation is a critical measure in advancing sustainable water management and agricultural production. However, TWW...
The use of treated wastewater (TWW) for agricultural irrigation is a critical measure in advancing sustainable water management and agricultural production. However, TWW irrigation in agriculture serves as a conduit to introduce many contaminants of emerging concern (CECs) into the soil-plant-food continuum, posing potential environmental and human health risks. Currently, there are few practical options to mitigate the potential risk while promoting the safe reuse of TWW. In this greenhouse study, the accumulation of 11 commonly occurring CECs was evaluated in three vegetables (radish, lettuce, and tomato) subjected to two different irrigation schemes: whole-season irrigation with CEC-spiked water (FULL), and half-season irrigation with CEC-spiked water, followed by irrigation with clean water for the remaining season (HALF). Significant decreases (57.0-99.8 %, p < 0.05) in the accumulation of meprobamate, carbamazepine, PFBS, PFBA, and PFHxA in edible tissues were found for the HALF treatment with the alternating irrigation scheme. The CEC accumulation reduction was attributed to reduced chemical input, soil degradation, plant metabolism, and plant growth dilution. The structural equation modeling showed that this mitigation strategy was particularly effective for CECs with a high bioaccumulation potential and short half-life in soil, while less effective for those that are more persistent. The study findings demonstrate the effectiveness of this simple and on-farm applicable management strategy that can be used to minimize the potential contamination of food crops from the use of TWW and other marginal water sources in agriculture, while promoting safe reuse and contributing to environmental sustainability.
PubMed: 38555786
DOI: 10.1016/j.watres.2024.121504 -
Journal of Analytical Toxicology Oct 2022A rapid, simple extraction method followed by qualitative screening using liquid chromatography-tandem mass spectrometry (LC-MS-MS) for drugs in oral fluid is presented....
A rapid, simple extraction method followed by qualitative screening using liquid chromatography-tandem mass spectrometry (LC-MS-MS) for drugs in oral fluid is presented. The decision points were selected to be at, or lower, than those recommended as Tier I compounds by the National Safety Council's Alcohol, Drugs and Impairment Division for toxicological investigation of driving under the influence of drug (DUID) cases and were also at, or lower, than those recommended by Substance Abuse and Mental Health Service Administration and the Department of Transportation for Federal workplace drug testing programs. The method included 30 drugs: delta-9-tetrahydrocannabinol, amphetamine, methamphetamine, 3,4-methylenedioxymethamphetamine, 3,4-methylenedioxyamphetamine, cocaine, benzoylecgonine, carisoprodol, meprobamate, zolpidem, alprazolam, clonazepam, 7-aminoclonazepam, diazepam, nordiazepam, lorazepam, oxazepam, temazepam, codeine, morphine, 6-acetylmorphine, buprenorphine, fentanyl, hydrocodone, hydromorphone, oxycodone, oxymorphone, methadone, tramadol and phencyclidine. Phencyclidine was included because it is in the Federal workplace program even though it is considered a Tier II drug for DUID cases. A liquid-liquid extraction method using isopropanol, hexane and ethyl acetate to extract drugs from the oral fluid-buffer mix collected in a Quantisal™ device, followed by LC-MS-MS screening, was developed and validated according to ANSI/ASB 2019 Standard Practices for Method Validation in Forensic Toxicology. Interference studies, limit of detection, precision at the decision point, ionization suppression/enhancement and processed sample stability were determined for each drug. The method was successfully applied to proficiency specimens and routine samples received in the laboratory.
Topics: 2-Propanol; 3,4-Methylenedioxyamphetamine; Alprazolam; Amphetamines; Buprenorphine; Carisoprodol; Clonazepam; Cocaine; Codeine; Dronabinol; Fentanyl; Hexanes; Hydrocodone; Hydromorphone; Lorazepam; Meprobamate; Methadone; Methamphetamine; Morphine Derivatives; N-Methyl-3,4-methylenedioxyamphetamine; Nordazepam; Oxazepam; Oxycodone; Oxymorphone; Pharmaceutical Preparations; Phencyclidine; Tandem Mass Spectrometry; Temazepam; Tramadol; Zolpidem
PubMed: 35640884
DOI: 10.1093/jat/bkac031 -
Journal of Clinical Medicine Feb 2022Centrally acting skeletal muscle relaxants (CMR) such as carisoprodol are used to treat acute, painful musculoskeletal conditions, though its precise mode of action has...
Carisoprodol Single and Multiple Dose PK-PD. Part II: Pharmacodynamics Evaluation Method for Central Muscle Relaxants. Double-Blind Placebo-Controlled Clinical Trial in Healthy Volunteers.
Centrally acting skeletal muscle relaxants (CMR) such as carisoprodol are used to treat acute, painful musculoskeletal conditions, though its precise mode of action has not been characterized. A double-blinded, placebo-controlled, randomized clinical trial was designed to evaluate the pharmacokinetics-pharmacodynamics (PKPD) of CMR after single (350 mg), double (700 mg), and multiple doses (up to 350 mg/8 h, 14 days) of carisoprodol. Muscular (Electromyogram-EMG, muscular strength dynamometry), central (sedation), and tolerability (psychomotor activity test, adverse events) parameters, as well as withdrawal symptoms, were evaluated. Thirteen healthy volunteers were enrolled. No evidence of direct muscle relaxation was evidenced, but some differences on sedation were evidenced throughout the study, suggesting that CMRs act, at least partly, through sedation. Most significant differences were detected at 1.5 h after dosing. The effect on psychomotor impairment was variable, most prominently after 1.5 h, too, suggesting that it is produced by carisoprodol rather than by meprobamate. No withdrawal symptoms were detected, so the risk of dependence following maximum doses and duration of treatment recommended, and under medical supervision, should be low.
PubMed: 35207414
DOI: 10.3390/jcm11041141 -
Journal of Clinical Medicine Feb 2022Carisoprodol was authorised in 1959 without a full pharmacokinetic-pharmacodynamic (PK-PD) characterisation. We designed a crossover, double-blind, placebo-controlled,...
Single and Multiple Dose PK-PD Characterization for Carisoprodol. Part I: Pharmacokinetics, Metabolites, and 2C19 Phenotype Influence. Double-Blind, Placebo-Controlled Clinical Trial in Healthy Volunteers.
Carisoprodol was authorised in 1959 without a full pharmacokinetic-pharmacodynamic (PK-PD) characterisation. We designed a crossover, double-blind, placebo-controlled, randomized clinical trial to characterize the PKs of carisoprodol and its main active metabolite, meprobamate, after single (350 mg), multiple (350 mg/8 h, 14 days), and double (700 mg) doses of carisoprodol. Thirteen healthy volunteers were enrolled. After a single (350 mg) dose, the main carisoprodol parameters were (mean ± SD) Cmax: 2580 ± 1214 ng/mL, AUC: 8072 ± 6303 h·ng/mL, and half-life (T): 2 ± 0.8 h. For meprobamate, the parameters were Cmax: 2181 ± 605 ng/mL and 34,529 ± 7747 h·ng/mL y 9 ± 1.9 h. Different profiles were found for extensive and poor 2C19 metabolizers. After 14 days of treatment (350 mg/8 h) the results for carisoprodol were (mean ± SD) Cmax: 2504 ± 730 ng/mL, AUC: 7451 ± 3615 h·ng/mL, and T: 2 ± 0.7 h. For meprobamate (a steady state was reached), the parameters were Cmax: 5758 ± 1255 ng/mL and 79,699 ± 17,978 h·ng/mL y 8.7 ± 1.4 h. The study allowed for the full characterization of the pharmacokinetic profile of carisoprodol and meprobamate. Accumulation of meprobamate but not of carisoprodol was evident after 14 days of treatment.
PubMed: 35160309
DOI: 10.3390/jcm11030858 -
Chemosphere Dec 2021Endorheic lakes (or terminal lakes, TLs) have no natural outlet other than evaporation and slow infiltration. Some TLs receive reclaimed wastewater which contains poorly...
Endorheic lakes (or terminal lakes, TLs) have no natural outlet other than evaporation and slow infiltration. Some TLs receive reclaimed wastewater which contains poorly removed trace organic contaminants (TrOCs). To determine if TLs accumulate TrOCs we conducted a preliminary assessment of the occurrence of ten TrOCs in three TLs receiving reclaimed wastewater and one TL which does not directly receive reclaimed wastewater. Five of ten TrOCs (carbamazepine, DEET, fluoxetine, primidone, and trimethoprim) were present in all four TLs' surface waters (~0.3-1109 ng/L), six (caffeine, carbamazepine, DEET, diphenhydramine, primidone, and trimethoprim) were present in sediment samples (0.1-77 ng/gDW) and in soil samples (0.1-137 ng/gDW). Concentrations of caffeine, carbamazepine, diphenhydramine, fluoxetine and meprobamate were significantly higher in TLs receiving wastewater from a secondary treatment plant compared to those TLs which received tertiary treated wastewater. Carbamazepine, fluoxetine, sulfamethoxazole, and trimethoprim were present at concentrations greater than is typical of other U.S. freshwater lakes, but other TrOC concentrations were present at lower concentrations than in other freshwater lakes. We conclude that some TrOCs may accumulate in TLs, but to a lesser extent than would be expected based on the accumulation of dissolved constituents alone, which indicates that there are other unidentified processes in TLs that contribute to TrOC losses. Other TLs across the globe may have similar levels of TrOCs due to anthropogenic influence and treated wastewater inputs.
Topics: Carbamazepine; Lakes; Sulfamethoxazole; Wastewater; Water Pollutants, Chemical
PubMed: 34242983
DOI: 10.1016/j.chemosphere.2021.131408 -
Analytical Methods : Advancing Methods... Jul 2021Pharmaceuticals and personal care products (PPCPs) can enter agricultural fields through wastewater irrigation, biosolid amendments, or urine fertilization. Numerous...
Pharmaceuticals and personal care products (PPCPs) can enter agricultural fields through wastewater irrigation, biosolid amendments, or urine fertilization. Numerous studies have assessed the risk of PPCP contamination, however there are no standardized methodologies for sample treatment, making the interpretation of results challenging. Various time periods between sampling and analysis have been reported (shipping, storage, etc.), but literature is lacking in the evaluation of PPCP degradation amidst this process. This study assessed the stability of 20 pharmaceuticals (200 μg L) in soil and crops stored at -40 °C for 7, 30, and 310 days. After 310 days, caffeine, meprobamate, trimethoprim, primidone, carbamazepine, anhydro-erythromycin and dilantin were found to be stable (≥75% recovery) in all matrices. On the other hand, acetaminophen, amitriptyline, bupropion, lamotrigine, sulfamethoxazole, naproxen, ibuprofen, and paroxetine were unstable after 30 days in at least one of the matrices investigated. Due to variations in analyte stability, fortification with isotopically-labelled surrogates at the point of sample collection was evaluated in comparison to fortification after shipment and storage, immediately prior to extraction. Chromatographic peak areas of stable analytes were found to be reproducible (±15%) in field-fortified samples, indicating that no additional error occurred during sample handling under field conditions despite having a less controlled environment. Unstable analytes revealed notable differences in peak areas between fortification times, suggesting that fortification immediately after sample collection is crucial to account for analyte losses during shipping and storage, resulting in accurate quantification of PPCPs.
Topics: Cosmetics; Pharmaceutical Preparations; Soil; Soil Pollutants; Wastewater
PubMed: 34142694
DOI: 10.1039/d1ay00623a -
Forensic Science International Apr 2021Concurrent use of opioids, benzodiazepines, and skeletal muscle relaxants potentiates the drug effect and respiratory depression via interactions of μ-opioid and GABA...
Concurrent use of opioids, benzodiazepines, and skeletal muscle relaxants potentiates the drug effect and respiratory depression via interactions of μ-opioid and GABA receptors. In the early 2000s when abuse of prescription drugs began to spike, a potent combination including hydrocodone, alprazolam, and carisoprodol, aka the "Houston Cocktail" or "Holy Trinity", emerged that may give users heroin-like euphoria. This research evaluated driving while intoxicated (DWI) cases that tested positive for hydrocodone, alprazolam, and carisoprodol, between 2015 and 2019. The blood samples were collected from drivers and submitted by the Houston Police Department (HPD). They were subsequently analyzed for alcohol and drugs by reference laboratories or Houston Forensic Science Center (HFSC). Toxicological findings, demographic information, and observed impairment were evaluated for the Houston Cocktail-positive DWI cases. A total of 80 DWI/DUID cases positive for hydrocodone, alprazolam, and carisoprodol in blood in which the traffic offense occurred between May 2015 and December 2019 were identified. Among these Houston Cocktail cases, the mean (median, range) concentrations were 75 (61, 6.9-322) ng/mL for hydrocodone, 58 (48, 5.8-180) ng/mL for alprazolam, and 3.9 (3.0, 0.3-14; n = 68) µg/mL for carisoprodol; 80 (100%) and 23 (29%) cases were also positive for meprobamate (mean 13; range 1.2-41 µg/mL) and hydromorphone (1.8; 1.0-3.3 ng/mL), respectively; carisoprodol and meprobamate in 12 of the cases were qualitatively detected. Forty six percent of those cases were females and 54% were males; 44% were Blacks, 46% were Whites, and 10% were other races as identified by the arresting officer. Mean (median) age of the drivers was 36 (34) years, ranged from 22 to 60 years. Twenty eight percent of the cases were positive for the Houston Cocktail only; 21% had one other drug/metabolite, 28% two, 14% three, and 10% had four or more additional drugs/metabolites. Of the 80 cases, cannabinoids were the most frequently detected analytes (35%), followed by codeine (11%). The drivers exhibited driving problems related to lane position, vigilance, judgment, speed, and/or braking. Many of the drivers (70-84%) had red/glassy eyes, slurred speed, poor balance, HGN and impaired divided attention. The present study showed that despite a traffic safety risk, drivers in Houston continue to use this dangerous drug combination. The risk is further exacerbated by the fact that the many drivers had yet other drugs in the system besides the three drugs.
PubMed: 33964487
DOI: 10.1016/j.forsciint.2021.110819 -
Epilepsia Mar 2021Since 1955, several alkyl-carbamates have been developed for the treatment of anxiety and epilepsy, including meprobamate, flupirtine, felbamate, retigabine,... (Comparative Study)
Comparative Study Review
Since 1955, several alkyl-carbamates have been developed for the treatment of anxiety and epilepsy, including meprobamate, flupirtine, felbamate, retigabine, carisbamate, and cenobamate. They have each enjoyed varying levels of success as antiseizure drugs; however, they have all been plagued by the emergence of serious and sometimes life-threatening adverse events. In this review, we compare and contrast their predominant molecular mechanisms of action, their antiseizure profile, and where possible, their clinical efficacy. The preclinical, clinical, and mechanistic profile of the prototypical γ-aminobutyric acidergic (GABAergic) modulator phenobarbital is included for comparison. Like phenobarbital, all of the clinically approved alkyl-carbamates share an ability to enhance inhibitory neurotransmission through modulation of the GABA receptor, although the specific mechanism of interaction differs among the different drugs discussed. In addition, several alkyl-carbamates have been shown to interact with voltage-gated ion channels. Flupirtine and retigabine share an ability to activate K currents mediated by KCNQ (Kv7) K channels, and felbamate, carisbamate, and cenobamate have been shown to block Na channels. In contrast to other alkyl-carbamates, cenobamate seems to be unique in its ability to preferentially attenuate the persistent rather than transient Na current. Results from recent randomized controlled clinical trials with cenobamate suggest that this newest antiseizure alkyl-carbamate possesses a degree of efficacy not witnessed since felbamate was approved in 1993. Given that ceno-bamate's mechanistic profile is unique among the alkyl-carbamates, it is not clear whether this impressive efficacy reflects an as yet undescribed mechanism of action or whether it possesses a unique synergy between its actions at the GABA receptor and on persistent Na currents. The high efficacy of cenobamate is, however, tempered by the risk of serious rash and low tolerability at higher doses, meaning that further safety studies and clinical experience are needed to determine the true clinical value of cenobamate.
Topics: Anticonvulsants; Carbamates; Chlorophenols; Epilepsy; Humans; Tetrazoles; Treatment Outcome
PubMed: 33580520
DOI: 10.1111/epi.16832