ABSTRACT
This study reports a fast and visual detection method of antidepressant sertraline (SRT) drug by the core-shell AuNPs@CDs as the nanoprobes. The CDs has been eco-friendly synthesized from sweet lemon wastes to directly reduce Au+ to AuNPs without any external photoirradiation process or additional reductants. Optimizing key variables that impact the sensing process has been done using the central composite design (CCD) approach to simulate the assay condition before the analysis. Adding SRT with different concentrations to the nanoprobes under mildly acidic conditions presents an absorbance peak at 560 nm with purple color tonalities that differ from the behavior of alone nanoprobes (530 nm, pink color). The obtained absorption change is linearly proportional to the increase of SRT concentration from 1 µM to 35 µM with a limit of detection (LOD) value of 100 nM. The color changes with a vivid tonality from pink and purple to violet as the colorful ï¬ngerprint patterns are readily traceable by the naked eye, allowing the visual assay of SRT. The greenness of the developed approach is well evaluated by some international indexes including the complimentary green analytical procedure (ComplexGAPI) and also, the analytical greenness (AGREE) indexes. The proposed waste-derived nanoprobes based on the eco-friendly procedure not only conduct quantitative and qualitative non-invasive analysis of SRT by the naked eye but also, may widen for other applications in various fields.
Subject(s)
Cadmium Compounds , Gold , Metal Nanoparticles , Sertraline , Sulfides , Gold/chemistry , Metal Nanoparticles/chemistry , Sertraline/analysis , Sertraline/chemistry , Sulfides/chemistry , Cadmium Compounds/chemistry , Citrus/chemistry , Colorimetry/methods , Limit of Detection , Antidepressive Agents/analysisABSTRACT
This study employed simple polystyrene-coated magnetite nanoparticles (PS@MNPs)-assisted batch adsorption process for the removal of two antidepressant active ingredients (amitriptyline HCl and sertraline HCl) from hospital wastewater. Dominant parameters of the adsorption process including pH, adsorbent amount, and contact period were optimized through the univariate approach to enhance the adsorption efficiency. Upon reaching optimum adsorption conditions, equilibrium experiments were performed by spiking the adsorbates in hospital wastewater in the concentration range of 100-2000 µg/L. The concentrations of the adsorbates in the effluent were calculated using the matrix-matching calibration strategy to enhance the accuracy of quantification. A validated switchable solvent-based liquid phase microextraction (SS-LPME) method was employed to enrich the two active pharmaceutical ingredients (APIs) prior to sensitive determination with GC-MS (gas chromatography-mass spectrometry). The equilibrium data were mathematically modeled employing the Langmuir and Freundlich adsorption isotherm models. The isotherm constants were calculated, and the results showed that both the isotherm models fitted well with the experimental data. The efficient and simple batch adsorption strategy reported in this study was successfully employed to remove amitriptyline HCl and sertraline HCl from hospital wastewater at low concentrations.
Subject(s)
Magnetite Nanoparticles , Water Pollutants, Chemical , Amitriptyline/analysis , Wastewater , Bulk Drugs , Polystyrenes/analysis , Sertraline/analysis , Adsorption , Magnetite Nanoparticles/chemistry , Environmental Monitoring , Antidepressive Agents/analysis , Water Pollutants, Chemical/analysis , Kinetics , Hydrogen-Ion ConcentrationABSTRACT
Wastewater treatment plants (WWTPs) are a major source of micropollutants to surface waters. Currently, their chemical or biological monitoring is realized by using grab or composite samples, which provides only snapshots of the current wastewater composition. Especially in WWTPs with industrial input, the wastewater composition can be highly variable and a continuous assessment would be advantageous, but very labor and cost intensive. A promising concept are automated real-time biological early warning systems (BEWS), where living organisms are constantly exposed to the water and an alarm is triggered if the organism's responses exceed a harmful threshold of acute toxicity. Currently, BEWS are established for drinking water and surface water but are seldom applied to monitor wastewater. This study demonstrates that a battery of BEWS using algae (Chlorella vulgaris in the Algae Toximeter, bbe Moldaenke), water flea (Daphnia magna in the DaphTox II, bbe Moldaenke) and gammarids (Gammarus pulex in the Sensaguard, REMONDIS Aqua) can be adapted for wastewater surveillance. For continuous low-maintenance operation, a back-washable membrane filtration system is indispensable for adequate preparation of treated wastewater. Only minor deviations in the reaction of the organisms towards treated and filtered wastewater compared to surface waters were detected. After spiking treated wastewater with two concentrations of the model compounds diuron, chlorpyrifos methyl, and sertraline, the organisms in the different BEWS showed clear responses depending on the respective compound, concentration and mode of action. Immediate effects on photosynthetic activity of algae were detected for diuron exposure, and strong behavioral changes in water flea and gammarids after exposure to chlorpyrifos methyl or sertraline were observed, which triggered automated alarms. Different types of data analysis were applied to extract more information out of the specific behavioral traits, than only provided by the vendors algorithms. To investigate, whether behavioral movement changes can be linked to impact other endpoints, the effects on feeding activity of G. pulex were evaluated and results indicated significant differences between the exposures. Overall, these findings provide an important basis indicating that BEWS have the potential to act as alarm systems for pollution events in the wastewater sector.
Subject(s)
Chlorella vulgaris , Chlorpyrifos , Water Pollutants, Chemical , Water Purification , Wastewater , Water Pollutants, Chemical/chemistry , Diuron , Sertraline/analysis , Wastewater-Based Epidemiological Monitoring , Environmental Monitoring/methodsABSTRACT
The occurrence of pharmaceuticals in the aquatic environment is a global water quality challenge for several reasons, such as deleterious effects on ecological and human health, antibiotic resistance development, and endocrine-disrupting effects on aquatic organisms. To optimize their removal from the water cycle, understanding the processes during biological wastewater treatment is crucial. Time-of-flight secondary ion mass spectrometry imaging was successfully applied to investigate and analyze the distribution of pharmaceuticals as well as endogenous molecules in the complex biological matrix of biofilms for wastewater treatment. Several compounds and their localization were identified in the biofilm section, including citalopram, ketoconazole, ketoconazole transformation products, and sertraline. The images revealed the pharmaceuticals gathered in distinct sites of the biofilm matrix. While citalopram penetrated the biofilm deeply, sertraline remained confined in its outer layer. Both pharmaceuticals seemed to mainly colocalize with phosphocholine lipids. Ketoconazole concentrated in small areas with high signal intensity. The approach outlined here presents a powerful strategy for visualizing the chemical composition of biofilms for wastewater treatment and demonstrates its promising utility for elucidating the mechanisms behind pharmaceutical and antimicrobial removal in biological wastewater treatment.
Subject(s)
Waste Disposal, Fluid , Water Pollutants, Chemical , Humans , Waste Disposal, Fluid/methods , Citalopram/analysis , Citalopram/pharmacology , Ketoconazole/analysis , Ketoconazole/pharmacology , Sertraline/analysis , Sertraline/pharmacology , Spectrometry, Mass, Secondary Ion , Water Pollutants, Chemical/analysis , Wastewater , Biofilms , Pharmaceutical PreparationsABSTRACT
Riverine fish in densely populated areas is constantly exposed to wastewater-borne contaminants from effluent discharges. These can enter the organism through the skin, gills or by ingestion. Whereas most studies assessing the contaminant burden in exposed fish have focused either on muscle or a limited set of tissues. Here we set out to generate a more comprehensive overview of the distribution of pollutants across tissues by analyzing a panel of matrices including liver, kidney, skin, brain, muscle, heart, plasma and bile. To achieve a broad analyte coverage with a minimal bias towards a specific contaminant class, sample extracts from four fish species were analyzed by High-Performance Liquid Chromatography (HPLC) - high-resolution mass spectrometry (HRMS) for the presence of 600 wastewater-borne pharmaceutically active compounds (PhACs) with known environmental relevance in river water through a suspect-screening analysis. A total of 30 compounds were detected by suspect screening in at least one of the analyzed tissues with a clear prevalence of antidepressants. Of these, 15 were detected at confidence level 2.a (Schymanski scale), and 15 were detected at confidence level 1 following confirmation with authentic standards, which furthermore enabled their quantification. The detected PhACs confirmed with level 1 of confidence included acridone, acetaminophen, caffeine, clarithromycin, codeine, diazepam, diltiazem, fluoxetine, ketoprofen, loratadine, metoprolol, sertraline, sotalol, trimethoprim, and venlafaxine. Among these substances, sertraline stood out as it displayed the highest detection frequency. The values of tissue partition coefficients for sertraline in the liver, kidney, brain and muscle were correlated with its physicochemical properties. Based on inter-matrix comparison of detection frequencies, liver, kidney, skin and heart should be included in the biomonitoring studies of PhACs in riverine fish.
Subject(s)
Body Fluids , Water Pollutants, Chemical , Animals , Wastewater , Sertraline/analysis , Water Pollutants, Chemical/analysis , Fishes , Body Fluids/chemistry , Pharmaceutical Preparations , Environmental MonitoringABSTRACT
Bioaccumulation of ionizable pharmaceuticals has been increasingly studied, with most reported aquatic tissue concentrations in field or laboratory experiments being from fish. However, higher levels of antidepressants have been observed in bivalves compared with fish from effluent-dominated and dependent surface waters. Such observations may be important for biodiversity because approximately 70% of freshwater bivalves in North America are considered to be vulnerable to extinction. Because experimental bioaccumulation information for freshwater bivalves is lacking, we examined accumulation dynamics in the freshwater pondmussel, Sagittunio subrostratus, following exposure to a model weak acid, acetaminophen (mean (±SD) = 4.9 ± 1 µg L-1 ), and a model weak base, sertraline (mean (±SD) = 1.1 ± 1.1 µg L-1 ) during 14-day uptake and 7-day depuration experiments. Pharmaceutical concentrations were analyzed in water and tissue using isotope dilution liquid chromatography-tandem mass spectrometry. Mussels accumulated two orders of magnitude higher concentrations of sertraline (31.7 ± 9.4 µg g-1 ) compared to acetaminophen (0.3 ± 0.1 µg g-1 ). Ratio and kinetic-based bioaccumulation factors of 28,836.4 (L kg-1 ) and 34.9 (L kg-1 ) were calculated for sertraline and for acetaminophen at 65.3 (L kg-1 ) and 0.13 (L kg-1 ), respectively. However, after 14 days sertraline did not reach steady-state concentrations, although it was readily eliminated by S. subrostratus. Acetaminophen rapidly reached steady-state conditions but was not depurated over a 7-day period. Future bioaccumulation studies of ionizable pharmaceuticals in freshwater bivalves appear warranted. Environ Toxicol Chem 2023;42:1183-1189. © 2023 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.
Subject(s)
Bivalvia , Unionidae , Water Pollutants, Chemical , Animals , Sertraline/analysis , Bioaccumulation , Acetaminophen , Fresh Water/chemistry , Fishes , Pharmaceutical Preparations , Water Pollutants, Chemical/analysisABSTRACT
Abstract Personalized medicine is gaining importance in pharmacotherapeutics as it allows tailoring the drug treatment to achieve the best patient response. Orodispersible film (ODF) is easy to formulate in hospitals, produces dose flexibility to suit an individual needs, particularly for patients suffer from swallowing issues or prohibited to take fluids. Sertraline Hydrochloride (SRT) was solubilized in several cosolvents, then different SRT ODFs based on five hydrophilic polymers namely; polyvinyl alcohol (PVA), hydroxylethyl cellulose (HEC), hydroxypropyl methylcellulose E5 LV (HPMC E5 LV), sodium alginate (NaAlg) and gelatin at two concentrations (2% and 4%) were developed and characterized. The outcomes were exposed to response surface analysis to obtain the desirability results to obtain the optimized formulation. Blended ODFs were developed from 4% PVA and 2% HEC in different blends and then potassium chloride (KCl) as a pore-forming agent was added to the best formulation to investigate its dissolution enhancement effect. F14 containing 4% PVA: 2% HEC 2:1 with 5% KCl showed best physicochemical properties of suitable pH (5.6), disintegration time (6 sec), good folding endurance which released 91 % SRT after 15 min. SRT ODF is an encouraging delivery system in the course of personalized medicine for the management of depression.
Subject(s)
Solvents , Sertraline/analysis , Precision Medicine , Excipients , Process OptimizationABSTRACT
Sertraline (SER) is one of the most frequently detected antidepressant drugs in aquatic environments. However, knowledge regarding SER-induced behavioral alterations in fish is insufficient, as well as the mechanisms underlying SER-induced toxicity. The present study aimed to determine behavioral and molecular responses in larval fish following SER exposure with a focus on its mode of action. Zebrafish embryos (~6 h-post-fertilization, hpf) were exposed to one of three concentrations of SER (1, 10, 100 µg/L) for 6 days, respectively. Evaluated parameters included development, behavior, transcripts related to serotonin signaling, serotonin levels, and acetylcholinesterase activity. Accelerated hatching of zebrafish embryos was observed for those fish exposed to 100 µg/L SER at 54 hpf. Locomotor activity (e.g. distance moved and mobile cumulative duration) was significantly reduced in larval zebrafish following exposure to 10 and 100 µg/L SER. Conversely, larval fish showed increased dark-avoidance after exposure to 1-100 µg/L SER. Of the measured transcripts related to serotonin signaling, only serotonin transporter (serta) and serotonin receptor 2c (5-ht2c) mRNA levels were increased in fish in response to 10 µg/L SER treatment. However, serotonin levels were unaltered in larvae exposed to SER. There were no differences among groups in acetylcholinesterase activity at any concentration tested. Taking together, the results evidenced that exposure to SER alters behavioral responses in early-staged zebrafish, which may be related to the abnormal expression of 5-ht2c. This study elucidates molecular responses to SER and characterizes targets that may be sensitive to antidepressant pharmaceuticals in larval fish.
Subject(s)
Antidepressive Agents/toxicity , Behavior, Animal/drug effects , Sertraline/toxicity , Water Pollutants, Chemical/toxicity , Zebrafish/physiology , Animals , Antidepressive Agents/analysis , Embryo, Nonmammalian/drug effects , Embryo, Nonmammalian/physiology , Locomotion/drug effects , Serotonin/metabolism , Sertraline/analysis , Signal Transduction/drug effects , Water Pollutants, Chemical/analysis , Zebrafish/growth & development , Zebrafish/metabolismABSTRACT
The growing consumption of pharmaceuticals in the human population and the insufficient efficiency of their elimination in waste water has a long-term negative impact on the environment of aquatic ecosystems, including the organisms that inhabit them. A significant contributor is the consumption of anti-depressants from the SSRI group, which corresponds to their increasing concentration in the environment. The aim of this work was to determine if antidepressant sertraline is able to be stored in fish organisms and to evaluate the content of residues in various body tissues. Rainbow trout (Oncorhynchuss mykkis) was selected as the test organism and was artificially exposed to the antidepressant for 1 month (concentrations 0; 4.2; 44 and 400 ng.g-1 sertraline in the feed). Liver, kidney, brain and muscle tissue biopsies samples were taken for analysis. Detection was performed using an Accela 1250 LC pump and an Accela autosampler coupled with a high-performance mass analyzer with a heated electrospray ionization source Q-Exactive Orbitrap, operating in positive ionization mode and in PRM mode (m/z 306.08108->275.03888 and 309.009991->275.03888 for sertraline and internal standard, respectively). The limit of quantification of the method was 0.1 ng.g-1 of sertraline and the calibration curve showed a good linearity up to 20 ng.g-1. From the collected data, amount of residues was found in the liver, kidney and brain. In contrast, the incidence of residues in muscle tissue was not detected in all groups, which is favorable from the point of view of fish meat consumption, by humans.
Subject(s)
Drug Residues/analysis , Oncorhynchus mykiss/metabolism , Selective Serotonin Reuptake Inhibitors/analysis , Sertraline/analysis , Spectrometry, Mass, Electrospray Ionization , Tandem Mass Spectrometry , Water Pollutants, Chemical/analysis , Animals , Body Burden , Tissue DistributionABSTRACT
Sertraline is an antidepressant drug that has been frequently reported in the aquatic environment and biota. While the research has mostly dealt with its occurrence and toxicity, there is a lack of information pertaining to its environmental transformation. The present study aimed to fill in these gaps by giving an insight into mechanisms of sertraline phototransformation in surface waters, which was recognized as the main transformation pathway for this contaminant. We performed photodegradation experiments in presence of photosensitizers or reaction quenchers to determine rate constants and used them to predict sertraline phototransformation kinetics by "Aqueous Photochemistry of Environmentally occurring Xenobiotics" (APEX) software. It was established that sertraline degrades by pseudo-first order kinetics mostly dominated by direct photolysis, while the presence of certain reactive species including â¢OH, CO3-⢠and 3CDOM* further accelerate the compound's breakdown rate. To validate the predicted results, sertraline-spiked surface water was irradiated by sunlight, where the half-life of sertraline at around 1.4 days was estimated. While following the photodegradation kinetics, we also identified five transformation products, of which three were determined in Slovenian surface waters. According to the ECOSAR toxicity prediction, these transformation products will either have comparable or lower toxicity than their parent compound.
Subject(s)
Sertraline/chemistry , Water Pollutants, Chemical/chemistry , Fresh Water/chemistry , Half-Life , Kinetics , Photochemical Processes , Photochemistry , Photolysis , Sertraline/analysis , Software , Sunlight , Water/chemistry , Water Pollutants, Chemical/analysis , XenobioticsABSTRACT
Neurotransmission plays an essential role during the central nervous system (CNS) development. During the last years, several studies based on the changes produced in neurotransmitters of aquatic organisms caused by pharmaceuticals have been reported. Daphnia magna, the aquatic ecotoxicological model organism, shares several of the neurotransmitters targeted by antidepressant and other neuro-active drugs with vertebrates. Therefore, a method based on liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) has been applied for the first time to study the levels of 41 neurotransmitters in Daphnia magna under the effect of four different neuro-active pharmaceuticals (sertraline, venlafaxine, duloxetine and fluoxetine). In addition, the performance of LC-HRMS was studied in terms of linearity, sensitivity, intra- and inter-day precision, and overall robustness. The developed analytical method using LC-HRMS is a new tool for neurotoxicology research using the Daphnia magna model. As a result, general differences on the concentrations of those neurotransmitters exposed to the mentioned pharmaceuticals were observed.
Subject(s)
Chromatography, High Pressure Liquid/methods , Daphnia/chemistry , Duloxetine Hydrochloride/toxicity , Fluoxetine/toxicity , Mass Spectrometry/methods , Neurotransmitter Agents/chemistry , Sertraline/toxicity , Venlafaxine Hydrochloride/toxicity , Animals , Aquatic Organisms/drug effects , Aquatic Organisms/growth & development , Aquatic Organisms/metabolism , Daphnia/drug effects , Daphnia/metabolism , Duloxetine Hydrochloride/analysis , Fluoxetine/analysis , Models, Animal , Neurotransmitter Agents/metabolism , Sertraline/analysis , Venlafaxine Hydrochloride/analysis , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/toxicityABSTRACT
The present study involved segmental testing of hair in two clinical cases with known dosage histories. Hair analysis confirmed the first patient's exposure to the prescribed sertraline and citalopram for several months. Citalopram was generally distributed along the hair shaft in accordance with the drug ingestion period. By contrast, "false" positive results were observed for sertraline in distal hair segments, corresponding to a period of no sertraline exposure, which may indicate incorporation from sweat or sebum, which transport the drugs along the hair surface. The second patient received various drugs during her treatment for brain cancer. Metoclopramide, morphine, oxazepam, paracetamol, sumatriptan, tramadol, and zopiclone, which had been part of the therapy, were all detected in the proximal hair segment. The results of these two cases indicated that results-especially concerning the time of drug intake-must be interpreted with caution and allow for the possibility of incorporation from sweat or sebum.
Subject(s)
Analgesics/analysis , Hair/chemistry , Hypnotics and Sedatives/analysis , Selective Serotonin Reuptake Inhibitors/analysis , Vasoconstrictor Agents/analysis , Acetaminophen/analysis , Adult , Antiemetics/analysis , Azabicyclo Compounds/analysis , Citalopram/analysis , Female , Forensic Toxicology , Hair/growth & development , Humans , Metoclopramide/analysis , Morphine/analysis , Oxazepam/analysis , Piperazines/analysis , Sertraline/analysis , Sumatriptan/analysis , Tramadol/analysisABSTRACT
Despite increasing prescription rates of antidepressants in pregnant and breastfeeding women over the past decades, evidence of drug exposure for neonates through lactation is very sparse. Concentrations of three antidepressants citalopram, sertraline, and venlafaxine were measured in maternal blood and breast milk in 17 women receiving antidepressant therapy during breastfeeding period. We also computed concentration-by-dose-ratios (C/D) and milk to serum (plasma) penetration ratios (M/P). Non-parametric tests were applied. Serum concentration of citalopram and daily dosage correlated positively while daily dosage and mother milk concentration did not (rho = 0.939, p = 0.005, and rho = 0.772, p > 0.05 respectively). A significant correlation was also found between serum and milk concentrations (rho = 0.812, p = 0.05). Venlafaxine daily dosage correlated positively with the active moiety milk concentration (rho = 0.949, p = 0.014). No significant correlations were reported for sertraline. The amount of antidepressant concentrations to which neonates may be exposed, assessed as absolute infant dose (AID), was particularly low with the highest median AID being 0.16 mg/kg/day for venlafaxine. No significant difference was detected for the M/P ratios between different drugs (p > 0.05), whereas the comparison of C/D ratios revealed lower values in the sertraline group, with the highest values reported for citalopram group (p = 0.007 for serum concentrations and p = 0.008 for mother milk). Findings suggest that breastfeeding under antidepressant treatment constantly exposes children with measurable drug concentrations. As daily dosage and serum concentration of the antidepressants did not predict drug concentrations in mother milk, measuring of drug concentrations in milk helps to quantify drug exposure during breastfeeding. More data-even data of drug concentrations in breastfed children-are needed to better assess the effects of drug exposure on children's development.
Subject(s)
Antidepressive Agents/pharmacokinetics , Milk, Human/chemistry , Adult , Antidepressive Agents/analysis , Breast Feeding/adverse effects , Child Development/drug effects , Citalopram/analysis , Citalopram/pharmacokinetics , Depression/drug therapy , Female , Humans , Infant , Milk, Human/metabolism , Pregnancy , Selective Serotonin Reuptake Inhibitors/analysis , Selective Serotonin Reuptake Inhibitors/pharmacokinetics , Serotonin and Noradrenaline Reuptake Inhibitors/analysis , Serotonin and Noradrenaline Reuptake Inhibitors/pharmacokinetics , Sertraline/analysis , Sertraline/pharmacokinetics , Venlafaxine Hydrochloride/analysis , Venlafaxine Hydrochloride/pharmacokinetics , Young AdultSubject(s)
Acetaminophen/analysis , Codeine/analysis , Meconium/chemistry , Sertraline/analysis , Substance Abuse Detection/methods , Acetaminophen/urine , Adult , Chromatography, Liquid , Codeine/urine , Female , Humans , Infant, Newborn , Maternal Exposure , Pregnancy , Sertraline/urine , Tandem Mass SpectrometryABSTRACT
Environmental contamination with pharmaceuticals has received growing attention in recent years. Several studies describe the presence of traces of drugs in water bodies and soils and their impacts on nontarget organisms including plants. Due to these facts investigations of the uptake and metabolism of pharmaceuticals in organisms is an emerging research area. The present study demonstrates the analysis of three selected antidepressants (sertraline, clomipramine, and trazodone) as well as metabolites and transformation products in a cress model (Lepidium sativum). Cress was treated with tap water containing 10 mg/L of the parent drugs. Employing an analytical approach based on high performance liquid chromatography coupled with quadrupole time of flight or Orbitrap mass spectrometry in MS and MS² modes, in total 14 substances were identified in the cress extracts. All three parent drugs were taken up by the cress and translocated from the roots to the leaves in specific patterns. In addition to this, eleven metabolite species were identified. They were generated by hydroxylation, demethylation, conjugation with amino acids, or combinations of these mechanisms. Finally, the inclusion of control cultures in the experimental setup allowed for a differentiation of "true" metabolites generated by the cress and transformation products generated by plant-independent mechanisms.
Subject(s)
Clomipramine/metabolism , Lepidium sativum/metabolism , Sertraline/metabolism , Tandem Mass Spectrometry/methods , Trazodone/metabolism , Antidepressive Agents/analysis , Antidepressive Agents/metabolism , Chromatography, High Pressure Liquid , Clomipramine/analysis , Metabolome , Plant Leaves/chemistry , Plant Leaves/metabolism , Plant Roots/chemistry , Plant Roots/metabolism , Sertraline/analysis , Trazodone/analysisABSTRACT
Sertraline (SRT) is a modern and relatively safe selective serotonin reuptake inhibitor often used in the treatment of depression. Monitoring the body levels of this drug and its active metabolite, N-desmethylsertraline (DSRT), permits optimizing the dosage and personalizing the treatment, especially in the case of severe adverse reactions or lack of response to the applied therapy. The determination of SRT and DSRT in diagnostic material, i.e., blood, plasma, urine and saliva, and also in biological material from deceased persons, requires a variety of sensitive and reliable analytical methods to determine both the total drug level (blood) as well as the level of the unbound form (saliva and urine). This paper presents a detailed literature review of the methods of SRT and DSRT isolation from biological material and analytical techniques used for their determination. These include extractive procedures such as solid phase extraction and microextraction as well as liquid-liquid extraction. We pay particular attention to the parameters taken into account during optimization of extraction, i.e., the effect of pH, type of solvent and composition of the solvents mixture, on washing various types of sorbents (hydrophobic, hydrophilic-lipophilic and ion exchange) and elution of analytes. We show the advantages and disadvantages of the extraction techniques in terms of efficiency and precision of extraction. We also discuss protein precipitation as one of the more recent methods of sample purification. In our presentation of the final determination techniques, i.e., HPLC, LC and GC, we focus on the type of detector (UV, nitric-phosphate, MS) as the basic factor determining the sensitivity, expressed as the limits of detection and quantification achieved by a given method.
Subject(s)
Selective Serotonin Reuptake Inhibitors/analysis , Sertraline/analogs & derivatives , Chromatography, Liquid , Humans , Mass Spectrometry , Saliva/chemistry , Sertraline/analysis , Solid Phase Extraction , Urine/chemistryABSTRACT
A simple, green and fast analytical method was developed for the determination of sertraline in tap and waste water samples at trace levels by using supportive liquid-liquid extraction with gas chromatography-mass spectrometry. Different parameters affecting extraction efficiency such as types and volumes of extraction and supporter solvents, extraction period, salt type and amount were optimized to get lower detection limits. Ethyl acetate was selected as optimum extraction solvent. In order to improve the precision, anthracene-D10 was used as an internal standard. The calibration plot of sertraline was linear from 1.0 to 1000 ng/mL with a correlation coefficient of 0.999. The limit of detection value under the optimum conditions was found to be 0.43 ng/mL. In real sample measurements, spiking experiments were performed to check the reliability of the method for these matrices. The spiking experiments yielded satisfactory recoveries of 91.19 ± 2.48%, 90.48 ± 5.19% and 95.46 ± 6.56% for 100, 250 and 500 ng/mL sertraline for tap water, and 85.80 ± 2.15% and 92.43 ± 4.02% for 250 and 500 ng/mL sertraline for waste water.
Subject(s)
Drinking Water/chemistry , Sertraline/analysis , Wastewater/chemistry , Water Pollutants, Chemical/analysis , Gas Chromatography-Mass Spectrometry , Limit of Detection , Liquid-Liquid Extraction , Reproducibility of Results , Solvents/chemistryABSTRACT
RATIONALE: This study is the first to measure and correlate sertraline concentrations in maternal blood, amniotic fluid and umbilical cord blood and account for distribution of the drug between these three compartments. METHODS: Concentrations of sertraline were measured in six mother infant pairs at the time of delivery. Data are provided as median values, first and third quartiles as well as ranges. To account for the penetration ratio into amniotic fluid and cord blood, the concentration of sertraline in both environments was divided by the concentration in maternal serum. Daily doses were correlated with maternal serum- and umbilical cord blood-concentrations, and serum levels were correlated with levels in amniotic fluid. RESULTS: The median daily dose of sertraline was 75mg (Q1: 43.75mg, Q3: 100mg; range 25-100mg). Amniotic fluid concentrations of sertraline strongly correlated with the daily dose (r=0.833, p=0.039) while neither maternal serum concentrations nor cord blood concentrations correlated with the daily dose (p>0.05). The median penetration ratio for sertraline into amniotic fluid was 0.57 (Q1: 0.28, Q3: 0.75; range: 0.22-0.88). The median penetration ratio into the fetal circulation, calculated on the basis of umbilical cord blood-concentrations, was found to be 0.36 (Q1: 0.28, Q3: 0.49; range: 0.17-0.65). CONCLUSIONS: Sertraline concentrations in amniotic fluid gave evidence that maternally administered sertraline is constantly accessible to the fetus via amniotic fluid in a manner not previously appreciated. A relatively low penetration into fetal circulation may contribute to a sufficient safety profile of sertraline during pregnancy although in our study APGAR Scores were relatively low in three infants. Our data support the important role of therapeutic drug monitoring in maintaining the safety of pregnant women and exposed infants.
Subject(s)
Amniotic Fluid/chemistry , Drug Monitoring , Fetal Blood/chemistry , Selective Serotonin Reuptake Inhibitors/analysis , Sertraline/analysis , Adult , Depressive Disorder/drug therapy , Female , Humans , Placenta/metabolism , Pregnancy/blood , Pregnancy Complications/drug therapy , Prospective Studies , Selective Serotonin Reuptake Inhibitors/administration & dosage , Selective Serotonin Reuptake Inhibitors/blood , Sertraline/administration & dosage , Sertraline/bloodABSTRACT
Although reports of pharmaceutical bioconcentration in aquatic organisms are increasing, less is known about trophic transfer in aquatic food webs. The bioaccumulation and trophodynamics of sertraline and fluoxetine, 2 selective serotonin reuptake inhibitors (SSRIs) frequently detected in aquatic environments, were tested by exposing constructed aquatic food chains to SSRIs under controlled laboratory conditions. Both of these ionizable, weak base pharmaceuticals showed lower bioaccumulation factors (BAFs) with increasing trophic level (i.e., no biomagnifications) in 2 3-level food chains (Acer platanoides, fed to Asellus aquaticus, in turn fed to Notonecta glauca or Pungitius pungitius). Mean sertraline BAFs in A. platanoides, A. aquaticus, N. glauca, and P. pungitus were 2200 L/kg, 360 L/kg, 26 L/kg, and 49 L/kg, respectively, and mean fluoxetine BAFs 1300 L/kg, 110 L/kg, 11 L/kg, and 41 L/kg, respectively. The weak influence of diet was further demonstrated by measured BAFs being equal to or lower than measured bioconcentration factors (BCFs). Organism lipid content was not positively correlated with BAFs, suggesting that other processes are driving interspecific differences in SSRI bioaccumulation. The empirically derived parameter values were introduced into a proposed bioaccumulation model, and a poor correlation was found between modeled and empirical BAFs (predicted r2 = -0.63). In conclusion, the apparent lack of biomagnification of these ionizable pharmaceuticals suggests that environmental concern should not necessarily focus only on higher trophic levels, but also on species showing high BCFs at any trophic level. Environ Toxicol Chem 2017;36:1029-1037. © 2016 SETAC.
Subject(s)
Antidepressive Agents/metabolism , Aquatic Organisms/metabolism , Fluoxetine/metabolism , Models, Theoretical , Sertraline/metabolism , Water Pollutants, Chemical/metabolism , Animals , Antidepressive Agents/analysis , Fluoxetine/analysis , Food Chain , Sertraline/analysis , Sweden , Water Pollutants, Chemical/analysisABSTRACT
A sensitive analytical method was developed for the determination of sertraline in commercial drug samples by using GC-MS. The selected-ion monitoring mode was used at the most sensitive m/z 274 to obtain a lower detection limit. LOD/LOQ values were obtained as 1.6/5.4 ng/mL for sertraline under the optimum conditions. The calibration plot was linear between 5.0 and 2000 ng/mL with the correlation coefficient of 0.9999. The validated method was successfully applied to three different brands of drug samples for both qualitative and quantitative measurement of sertraline. In this experiment, four replicate extractions were performed for each brand, and the results were compared to the values written on the labels of the drug brands. Spiking experiments were also performed to check the effect of the matrixes on the determination, and it was observed that there was no shift in the retention time of the analyte. In addition, simulated gastric juice experiments were performed to check the stability of sertraline in the stomach for 240 min, and it was observed that there was no change in the structure of the analyte.