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Enantiomers of a chiral active pharmaceutical ingredient (API) often exhibit different physicochemical, pharmacokinetic, and biological properties. Therefore, enantioseparation becomes a critical aspect of pharmaceutical development. Sertraline, one of the most widely prescribed antidepressant medications, requires purification from its chiral impurities, and this is recommended and essential for its quality control. This perspective highlights the current established research on the separation and quantification of sertraline's chiral impurities, with a focus on instrumental and crystallization-based techniques., (© 2024 John Wiley & Sons Ltd.)

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 fingerprint 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., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (© 2023 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

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.

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., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

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.

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 • OH, CO 3 -• and 3 CDOM* 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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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.

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.

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., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

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.

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 r 2  = -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., (© 2016 SETAC.)

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., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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.

Polymer membrane and chemically modified carbon paste (CMCP) sensors for determination of sertraline HCl (Ser-Cl) incorporating sertraline tetraphenylborate (Ser-TPB) as an electro-active material were constructed. They showed a rapid and linear response for Ser-ion over the concentration range 0.01-10.00 mmol L(-1). The limits of detection were 2.80 and 9.55 μmol L(-1), and Nernastian slopes were 56.60, 59.60 mV decade(-1) for membrane and CMCP sensors for batch method. In flow injection analysis (FIA), the electrodes revealed comparatively good selectivity for Ser-ion with regard to a wide variety of different cations, sugars, and amino acids. The addition of different anionic additives, namely sodium tetraphenylborate (NaTPB), potassium tetraphenylborate (KTPB), potassium tetrakis[3,5-bis-(triflouromethyl)phenyl]borate (KTFMPB), and sodium tetrakis[3,5-bis(trifluoro-methyl)phenyl]borate (NaTFMPB), to the prepared mixture improved their response characteristics. The surface morphologies of membrane films containing PVC only (blank), plasticizer+PVC, Ser-TPB+plasticizer+PVC, and Ser-TPB +plasticizer+PVC+additive were studied using scanning and atomic force electron microscopes. These sensors had been used in the potentiometric titration of Ser-ion against NaTPB. Standard addition method for the pure raw material and some of its pharmaceutical tablets was used for Ser-Cl determination. The obtained results were tested for their repeatability and reproducibility and were statistically treated by F- and t- tests., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The penicillin sub-class of β-lactam antibiotics has not been examined for its enantiodiscriminating abilities in capillary electrophoresis (CE) until date. The present work was therefore designed to evaluate penicillin G potassium salt (PenG) as an ion-pair chiral selector (CS) using CE for its several attributes, namely, high solubility in water and lower alcohols, structure allowing multiple interactions with analytes and cost-effectiveness. Systematic experiments were performed to investigate the effect of composition of background electrolyte, applied voltage and capillary temperature on chiral separation. Baseline resolutions of enantiomers of five basic chiral drugs (namely, darifenacin, citalopram, sertraline, propranolol and metoprolol) were attained using a background electrolyte composed of water:methanol (90:10, v/v) and consisting of 10.7 or 16.1mM CS at 20°C using an applied voltage of 5kV., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Sertraline (Zoloft) is a selective serotonin reuptake inhibitor that is a commonly prescribed drug for the treatment of depression, obsessive-compulsive disorder, panic disorder, social anxiety disorder, premenstrual dysphoric disorder and post-traumatic stress disorder. Although the use of sertraline is relatively safe, certain side effects may negatively affect a pilot's performance and become a factor in an aviation accident. The authors' laboratory investigated the distribution of sertraline and its primary metabolite, desmethylsertraline, in various postmortem tissues and fluids obtained from 11 fatal aviation accident cases between 2001 and 2004. Eleven specimen types were analyzed for each case, including blood, urine, vitreous humor, liver, lung, kidney, spleen, muscle, brain, heart and bile. Human specimens were processed utilizing solid-phase extraction, followed by characterization and quantitation employing gas chromatography-mass spectrometry. Whole blood sertraline concentrations obtained from these 11 cases ranged from 0.005 to 0.392 µg/mL. The distribution coefficients of sertraline, expressed as specimen/blood ratio, were as follows: urine, 0.47 ± 0.39 (n = 6); vitreous humor, 0.02 ± 0.01 (n = 4); liver, 74 ± 59 (n = 11); lung, 67 ± 45 (n = 11); kidney, 7.4 ± 5 (n = 11); spleen, 46 ± 45 (n = 10); muscle, 2.1 ± 1.3 (n = 8); brain, 22 ± 14 (n = 10); heart, 9 ± 7 (n = 11); and bile, 36 ± 26 (n = 8). Postmortem distribution coefficients obtained for sertraline had coefficients of variation ranging from 47-99%. This study suggests that sertraline likely undergoes significant postmortem redistribution.

Sertraline is a widely-used antidepressant that is one of the selective serotonin reuptake inhibitors. It has been detected in biosolids and effluents from sewage treatment plants. Since sertraline can reach agriculture land through the application of municipal biosolids or reclaimed water, the persistence and dissipation pathways of (3)H-sertraline were determined in laboratory incubations using three agriculture soils varying in textures and properties. The total solvent extractable radioactivity decreased in all three soils with times to dissipate 50% of material (DT50) ranging from 48.1±3.5 (loam soil) to 84.5±13.8 (clay soil) days. Two hydroxylated sertraline transformation products were identified in all three soils by high performance liquid chromatography with time-of-flight mass spectrometry (HPLC-TOF-MS), but the accumulation did not exceed 10% of the initial parent concentration. The addition of liquid municipal biosolids to the loam soil had no effect on the rate of sertraline dissipation, or production of transformation products. In summary, sertraline was persistent in agricultural soils with major dissipation pathways including the production of non-extractable soil-bound residues, and accumulation of hydroxylated transformation products. The biologically active sertraline transformation product norsertraline was not detected in soil., (Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.)

We attempted the simultaneous determination of 5 drugs, mirtazapine, sertraline, chlorpromazine, amoxapine and zolpidem, detected in a gas chromatography-mass spectrometry screening test in an autopsy case. The solid-phase extraction of the analytes from biological samples was achieved using Oasis(®)HLB cartridges (Waters, Milford, MA, USA). Gas chromatography was performed on a HP-5MS fused silica capillary column (30 m × 0.25 mm i.d., 0.25 μm film thickness, Agilent Technologies). The mass spectrometer was operated with an electron energy of 70 eV in electron impact mode. The qualitative and quantitative analyses were performed in full-scan mode and the selected ion monitoring mode, respectively. The total ion chromatogram showed good separation of these drugs. Linear graphs were obtained with good correlation coefficients for these drugs from 0.001 to 2.0 μg/mL (r(2)=0.9909-0.9986) using imipramine-d6 as an internal standard. The recoveries of these drugs were found to be 62.8-88.0% in spiked whole blood. Mirtazapine, sertraline, chlorpromazine, amoxapine and zolpidem were found in post-mortem samples of the deceased at concentrations of 2.67, 0.07, 0.25, 0.32 and 0.68 μg/mL, respectively. The concentration of mirtazapine was within the lethal level and those of amoxapine and zolpidem were within the toxic level. We diagnosed that the cause of death was acute multiple drug poisoning. The simple and practical procedure used in this study is useful for the simultaneous determination of psychotropic drugs of various types in post-mortem biological samples., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Sertraline is a commonly prescribed selective inhibitor of serotonin uptake used for the treatment of mental depression and anxiety. Central blood and liver concentrations of sertraline (norsertraline) are compared to levels in peripheral blood in nine medical examiner cases. Specimens were initially screened for alcohol and simple volatiles by GC-FID headspace analysis, ELISA for drugs of abuse, and alkaline drugs by GC/MS. Sertraline, when detected by the alkaline drug screen, was subsequently confirmed and quantified by a specific GC-NPD procedure. Data suggest that when ingested with other medications, sertraline may be a contributing factor in death. Sertraline (norsertraline) concentrations ranged from 0.13 (0.11) to 2.1 (6.0) mg/L in peripheral blood, from 0.18 (0.12) to 2.0 (6.7) mg/L in central blood, and 21 to 160 mg/kg in liver. Sertraline central blood to peripheral blood ratios averaged 1.22±0.85 (mean±standard deviation). The liver to peripheral blood ratios, on the other hand, were markedly higher and averaged 97±40 (mean±standard deviation). Given that a liver to peripheral blood ratio exceeding 20 is indicative of propensity for significant postmortem redistribution, these data confirm that sertraline is prone to marked postmortem redistribution., (Published by Elsevier Ireland Ltd.)

A novel method for the determination of sertraline using dispersive liquid-liquid microextraction (DLLME) coupled with capillary electrophoresis (CE) was developed. Acetone and dichloromethane were used as the disperser solvent and extraction solvent, respectively. A mixture of the extraction and disperser solvents was rapidly injected into a 1.0 mL aqueous sample to form a cloudy solution. After the extraction, sertraline was analyzed using CE that was equipped with UV detection. A 74-fold improvement in the sensitivity was observed when DLLME was used to extract sertraline. Since the DLLME extract residue was redissolved with 5 μL of water that contained 20% methanol, the detection sensitivity was further enhanced through the use of field-amplified sample stacking (FASS). A 11-fold improvement in the sensitivity was obtained when FASS was used to on-line concentrate sertraline. Under optimal extraction and stacking conditions, the calibration curve, which ranged from 0.01 to 1 μM was observed to be linear. The limit of detection (LOD) at a signal-to-noise ratio of 3 was 2.5 nM for sertraline. An approximately 814-fold improvement in the sensitivity was observed for sertraline compare with injection of standard solution without the DLLME and FASS procedures. This developed method was successfully applied to the determination of sertraline in human urine samples., (Copyright © 2012 Elsevier B.V. All rights reserved.)

This paper presents two procedures for the determination of four selective serotonin reuptake inhibitors (citalopram, paroxetine, fluoxetine, and sertraline) and one metabolite (norfluoxetine) in sewage sludge utilizing three-phase hollow fiber liquid-phase microextraction (HF-LPME). First, direct HF-LPME was used for extraction, clean-up, and preconcentration. The pharmaceuticals were extracted from slurry samples into an organic phase and then back-extracted into an aqueous phase in the lumen of the hollow fiber. Second, a procedure combining pressurized hot water extraction and HF-LPME for clean-up and preconcentration was developed for the same analytes and matrix. The extracts were subsequently analyzed by liquid chromatography-mass spectrometry. For direct HF-LPME, limits of detection were between 1 and 12 ng g(-1) (dry weight) and the relative standard deviation (RSD) values were 3-12%. For the second method, limits of detection were approximately 6 ng g(-1) for all the compounds and RSD values were 8-12%. The methods were validated by comparison of results for the same samples. Sewage sludge from a Swedish wastewater treatment plant was analyzed by both methods; average concentrations were similar for citalopram, paroxetine, and fluoxetine with values of approximately 530, 40, and 200 ng g(-1) , respectively., (© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Climatological influences on site-specific ecohydrology are particularly germane in semiarid regions where instream flows are strongly influenced by effluent discharges. Because many traditional and emerging aquatic contaminants, such as pharmaceuticals, are ionizable, we examined diel surface water pH patterns (i.e., change in pH over a 24-h period) at 23 wadeable streams in central Texas, USA, representing a gradient of nutrient enrichment during consecutive summers of 2006 and 2007. The years of our study were characterized by decidedly different instream flows, which likely affected production:respiration dynamics and led to distinctions in diel pH patterns between 2006 and 2007. Site-specific ambient water quality criteria for NH(3) and the aquatic toxicity of the model weak base pharmaceutical sertraline were predicted using continuous water quality monitoring data from the sites. Drought conditions of 2006 significantly increased (p<0.05) diel pH changes compared to high instream flows of 2007,and the magnitude of diel pH variability was most pronounced at nutrient-enriched sites in 2006. Differences in diel pH change patterns between 2006 and 2007 affected predictions of the environmental fate and effects for model weak base pharmaceuticals and NH(3). Overall, site-specific diel pH was more variable at some sites than the difference in mean surface water pH between the 2 summers. Diel pH variability affected regulatory criteria, because 20% of the study sites in 2006 experienced greater than 5-fold differences in National Ambient Water Quality Criteria for NH(3) over 24-h periods. Our study emphasizes the potential uncertainty that diel pH variability may introduce in site-specific assessments and provides recommendations for environmental assessment of ionizable contaminants., (Copyright © 2011 SETAC.)

We present an environmental risk assessment of three selective serotonin reuptake inhibitors (SSRIs; citalopram, sertraline, and fluoxetine) in the aquatic environment based on two case scenarios. Abiotic and biotic degradation experiments and sorption estimates were used to predict environmental concentrations of three SSRIs from the wastewater of two psychiatric hospitals, the primary sector, and wastewater entering and leaving wastewater treatment plants (WWTPs). Assuming a sewage treatment retention time of 8 h, abiotic degradation was low, for all three SSRIs inhibitors, ranging between 0 and 2% for hydrolysis and 0 and 6% for photolysis. The biodegradation was also slow, ranging from 0 to 3% within an 8-h period. In untreated sewage, citalopram (CIT) and sertraline (SER) concentrations may be high enough to exert effects on the aquatic biota (CIT: 0.19-10.3 µg/L; SER: 0.14-17.1 µg/L). Removal of the pharmaceuticals is due primarily to sorption in the WWTP. Sertraline was estimated to have the highest concentrations in the sewage effluents, 4.4 and 19.9 ng/L for the two cases, respectively. In treated wastewater, individual SSRI concentrations are probably too low to exert effects on biota. By using concentration addition, a cocktail exposure scenario was estimated. The predicted concentration in the biota calculated from the cocktail effect was 0.05 and 0.16 nmol/g for the two cases, respectively, and SER was found to give the highest contribution to this cocktail effect. The results indicate that the concentrations in the wastewater effluents are one to two orders of magnitude lower than the concentrations likely to cause an effect in the aquatic biota., (© 2010 SETAC.)

In this study, a screening on reversed-phase stationary phases (including C(8), C(18), CN, PEG and amide) was carried out in order to obtain an efficient HPLC method for the determination of sertraline and three of its more closely related synthetical and non-chiral impurities, without using ion-pair reagents. The best results in terms of both retention time and resolution of the target analytes were obtained with a Zorbax Bonus-RP column, which contains a polar amide group embedded in a C(14) alkyl chain. Once the most suitable stationary phase was chosen, the HPLC method was optimized by using a factorial design, evaluating three quantitative factors (column temperature, buffer pH and buffer concentration) in order to find the best conditions which maximize the resolution between impurities A and B (positional isomers) and minimize the total run time. The final HPLC conditions were set by means of a second experimental design, which allowed optimizing the effects of the buffer pH and the proportion of methanol in the mobile phase. The optimal conditions for simultaneously determining sertraline and its impurities, being baseline separated in less than 10 min, were finally obtained with Zorbax Bonus-RP column (150 mmx4.6mm, 5 microm), under isocratic conditions with phosphate buffer (pH 2.8; 10mM)-methanol (63:37, v/v) at 50 degrees C, at the flow-rate of 1.0 mL/min. UV detection was set at 220 nm. This method was successfully validated following ICH guidelines and it proved to be reliable for the determination of sertraline and related impurities in tablets as pharmaceutical forms.

A capillary modified by assembling a molecular film was presented for the chiral separation of sertraline by microemulsion electrokinetic chromatography. The assembling molecular film was constructed with poly(diallyldimethylammonium-chloride) and β-cyclodextrin via inclusion complexation. The separation efficiency of cis-trans isomers and enantiomers of sertraline was improved with a running microemulsion that contained the acetonitrile, sodium dodecyl sulfate, n-butanol and n-hexane buffered with sodium tetraborate. The baseline separation of four sertraline cis-trans isomers and enantiomers was achieved under the optimum conditions. The detection limit for isomers and enantiomers of sertraline (1S,4S, 1R,4R, 1S,4R, 1R,4S) was 0.15, 0.15, 0.30, 0.30 mg/L, respectively. The mechanism of chiral separation was studied and it could be applied for the determination of commercial Zoloft tablet samples satisfactorily.

A reversed-phase high-performance liquid chromatographic (HPLC) method was developed and validated for evaluating the chiral discrimination ability of CYCLOBOND I 2000 DM chiral stationary phase (CSP) towards sertraline and its related enantiomers. The effect of pH, buffer concentration as well as nature of organic modifier, flow rate and temperature on enantioselectivity was investigated. The developed reversed-phase chromatographic conditions were able to separate not only the enantiomers of sertraline but also its process related chiral impurities. The method was validated for determination of enantiomeric purity of sertraline HCl in drug substances and formulations.

Sertraline is a widely used antidepressant belonging to the selective serotonin reuptake inhibitor class; its efficacy has been demonstrated not only in the treatment of major depression, obsessive compulsive and panic disorders, but also for eating, premenstrual dysphoric and post-traumatic stress disorders. Several methods have been published for the determination of sertraline in pharmaceuticals, biological materials and environmental samples. The purpose of the current review is to provide a systematic survey of the latest analytical techniques for the determination of sertraline covering the period from 1987 until 2008.

The objective of the current study was to develop a validated stability-indicating high-performance liquid chromatographic method for alprazolam and sertraline in combined dosage forms. The method was validated by subjecting the drugs to forced decomposition under hydrolysis, oxidation, photolysis, and thermal stress conditions prescribed by the International Conference on Harmonization. The drugs were successfully separated from major and minor degradation products on a reversed-phase C18 column by using 75 mM potassium dihydrogen phosphate buffer (pH 4.3)-acetonitrile-methanol (50 + 45 + 5, v/v/v) as the mobile phase with determination at 227 nm. The flow rate was 0.9 mL/min. The method was validated with respect to linearity, precision, accuracy, system suitability, and robustness. The responses were linear over the ranges of 1-80 and 5-200 microg/mL for alprazolam and sertraline, respectively. The recoveries of both drugs from a mixture of degradation products were in the range of 97-101%. The utility of the procedure was verified by its application to marketed formulations that were subjected to accelerated stability studies. The method distinctly separated the drugs and degradation products, even in actual samples. The products formed in marketed tablets were similar to those formed during stress studies.

A new simple, sensitive, and reproducible high-performance thin-layer chromatography method for the estimation of alprazolam and sertraline in combination is developed using silica gel plates with fluorescent indicators. The system is equipped with an automated sample applicator, and the detection was performed at 254 nm by using UV absorption densitometry. The mobile phase consists of carbon tetrachloride, methanol, acetone, and ammonia in the ratio 12:3:5:0.1. The retention factor values for alprazolam and sertraline are found to be 0.52 and 0.70, respectively. The limit of detection of alprazolam and sertraline in the mixture of given proportion is observed to be 0.05 microg/mL and 2.5 microg/mL and the limit of quantitation is 0.2 microg/mL and 10 microg/mL, respectively. The method has shown good linearity in the range of 0.2 microg/mL to 0.65 pg/mL for alprazolam (R2 > 0.9953) and 10 pg/mL to 32.5 microg/mL for sertraline (R2 > 0.9942). The intra- and inter-assay (n=5) variations in the linear range are less than 4% for alprazolam and 6% for sertraline. Three pharmaceutical products containing this combination are analyzed to test the applicability of the new method. The percentage of alprazolam and sertraline in the tablets studied range from 97.7% to 102.82% and 96.5% to 99.9%, respectively.

Sertraline is selective serotonin reuptake inhibitor drug marketed as Zoloft by Pfizer and used mainly for the treatment of depression, anxiety and obsession. A number of side effects are associated with the use of the drug including gastrointestinal complaints, nervousness and sexual dysfunction. This means that a reliable fast method (such as biosensing) for determining sertraline metabolic profile of patients is essential for adequate dosing. Nanobiosensor for the determination of sertraline biotransformation was prepared with cytochrome P450-2D6 (CYP2D6) and poly(8-anilino-1-napthalene sulphonic acid) nanotubes (90 nm in diameter and 600-800 nm in length) potentiodynamically deposited on gold. The biosensor gave a linear response over the concentration range of 0.2 and 1.4 microM with a sensitivity value of 0.301 microA/microM and a detection limit of 0.13 microM. The nanobiosensor exhibited substrate inhibition response profile for sertraline biotransformation at high concentrations. Analysis of the Michaelis-Menten region of the nanosensor response curve for sertraline gave an apparent Michaelis-Menten constant (K(m)) value of 0.75 microM, which is higher than the peak plasma concentration (C(max)) value of 0.55 microM, thereby making the sensor suitable for sertraline determination in serum.

Zoloft (sertraline hydrochloride) is one of the antidepressant medications used to treat depression, obsessive-compulsive disorder, and social anxiety disorder. The practice of embalming a cadaver is common, yet it may create problems for forensic toxicologists if the case was not previously suspected to involve drug overdose. According to the Eschweiler-Clarke reaction, drugs containing a secondary amine group react with formaldehyde to give N-methyl derivatives. Sertraline has a secondary amine group; therefore, we predicted that it may react with formalin to give N-methyl derivatives. The stability of sertraline in formalin solution was studied at three different concentrations (5%, 10%, and 20%) and at three different pHs (3.0, 7.0, and 9.5) for a period of 30 days. Setraline and its degraded products were extracted by liquid-liquid extraction using chloroform, and the concentrated extracts were analyzed by gas chromatography-mass spectrometry using electron impact ionization mode. The rate of conversion is rapid at higher pH. Sertraline was totally converted to the N-methyl derivative after 30 days in 10% and 20% formalin solutions at neutral and basic conditions. Therefore, forensic toxicologists should be cautious when performing a death investigation if formalin solution is the only sample available for analysis. This work shows that analysis for parent drug or its N-methyl derivative may provide data that will reduce the likelihood of false negatives.

Simple and reproducible spectrophotometric methods have been developed for determination of sertraline, fluoxetine, and venlafaxine in pharmaceutical preparations. The methods are based on the reactions between the studied drug substances and ion-pair agents (bromothymol blue, bromocresol green, or bromophenol blue) to produce yellow-colored ion-pair complexes in acidic buffers. After extracting in chloroform, the ion-pair complexes are spectrophotometrically determined at the optimum wavelength. Optimizations of the reaction conditions were carried out. Beer's law was obeyed within the concentration range from 1 to 15 microg/mL. The molar absorptivity, Sandell sensitivity, and detection and quantification limits were also determined. The developed methods were applied successfully for the determination of these drugs in some available commercial preparations. The results were compared statistically with those obtained from reported high-performance liquid chromatography methods.

An analytical method for quantification of the selective serotonin reuptake inhibitors (SSRIs) citalopram, sertraline, paroxetine, fluoxetine and fluvoxamine in sewage influents and effluents from selected sewage treatment plants (STPs) has been developed and validated. This quantification method is based on solid phase extraction of 2.5L samples, followed by liquid-liquid extraction for further sample clean up in order to minimize matrix effects during subsequent quantification. The samples were analysed on a high performance liquid chromatograph coupled to a triple quadrupole mass spectrometric detector using 0.1% ammonia in acetonitrile/water as mobile phase, with positive electrospray ionisation and multiple reaction monitoring for detection and quantification. 1-[3-(10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5-ylidene)propyl]-pyrrolidine (N-7084) was used as internal standard for quantification. The recovery rates of the SSRIs ranged between 54 and 84%, and the method limit of quantification (MLQ) was between 120 and 290 pg/L for the target compounds. Samples were collected in July 2005 from three different STPs and a pump station in Tromsø, Northern Norway. Two of the STPs serve the University hospital and its psychiatric department, respectively, in addition to domestic sewage. SSRIs were detected in all samples collected. The concentrations varied greatly from below the MLQ to several hundreds ng/L. Concentrations in influents were higher compared to filtered effluents, indicating that SSRIs adsorb to particulate matter, are degraded by microorganisms, or degraded in other ways during the filtration process. However, more samples should be analysed before general conclusions can be drawn.

The electrospray ionisation ion trap tandem mass spectrometry (ESI-MS(n)) of selected antidepressant drugs, i.e., citalopram, fluoxetine, mirtazapine, paroxetine, sertraline, and venlafaxine, has been investigated. Sequential product ion fragmentation experiments (MS(n)) have been performed in order to elucidate the degradation pathways for the [M+H](+) ions and their predominant product ions. These MS(n) experiments show certain characteristic fragmentations in that functional groups are generally cleaved from the ring systems as molecules such as H(2)O, amines and phenols. When an aromatic entity is present in a drug molecule together with a nitrogen-containing saturated ring structure as with mirtazapine, fragmentation initially occurs at the latter ring with the former being predictably resistant to fragmentation. Also, when an amine-containing drug molecule such as fluoxetine also contains a functional group, which liberates a phenol with a significantly lower DeltaH(f) (0) value than that of the corresponding amine, the phenol is preferentially liberated. The structures of product ions proposed for ESI-MS(n) can be supported by electrospray ionisation quadrupole-time-of-flight tandem mass spectrometry (ESI-QToF-MS/MS). These molecules can be identified and determined in mixtures at low ng/mL concentrations by the application of high-performance liquid chromatography/electrospray ionisation tandem mass spectrometry (HPLC/ESI-MS(2)), which can also be used for their analysis in hair samples., (Copyright (c) 2006 John Wiley & Sons, Ltd.)

Determining the enantiomeric purity of chiral therapeutic agents is important in the development of active pharmaceutical ingredients (API). A strategy for determining the enantiomeric purity of three APIs was developed using nuclear magnetic resonance (NMR) and the chiral solvating agent (CSA) 1,1-bi-2-naphthyl (1). While chiral chromatography is widely used to evaluate enantiomeric purity, it can sometimes suffer from tedious sample preparation obviating rapid measurements that are sometimes needed during the manufacture of such agents. The techniques described herein provide comparable enantiomeric purity results with those obtained with traditional chiral HPLC and other published methods for these compounds. Chiral analysis of standard samples of methylbenzylamine enantiomeric mixtures using 1 were found to be quantitative to approximately 1% minor enantiomer. Enantiomeric purity determination by NMR utilizing chiral solvating agents do not require special instrumental techniques, chemical derivatization or standards and is therefore ideally suited for rapid routine analysis. As a result, the technique demonstrated is commonly used in our laboratory as a complementary or alternative method to chiral HPLC or optical rotation measurements for routine determination of enantiomeric purity., (Copyright (c) 2005 John Wiley & Sons, Ltd.)

A flow injection square wave cathodic stripping voltammetric method has been developed for the determination of sertraline in a pharmaceutical preparation. The method shows linearity between peak current intensity and sertraline concentration for the interval between 0.20 x 10(-6) and 1.20 x 10(-6) mol L(-1). Limits of detection and quantification were found to be 1.5 x 10(-7) and 5.0 x 10 (-7) mol L(-1), respectively. Up to 70 samples per hour can be analysed with a good precision (R.S.D. = 2.5%). The proposed method was successfully applied to the determination of sertraline in a commercial product. In the voltammetric determination of sertraline in flow, a high sample rate is obtained at reduced costs, opening the possibility to compete with the chromatographic methods generally used for this analysis.

The exposure and fate of selective serotonin reuptake inhibitors (SSRIs) was evaluated using modeled predicted environmental concentrations (PECs) according to the U.S. and the European Union (EU) guidelines and microcosm model ecosystems. According to the U.S. guidance, crude environmental introduction concentrations, the only SSRI that would require environmental assessment would be sertraline. However, the more conservative EU draft guidance PEC would require further assessment of all five SSRIs. Refined PECs developed using the U.S. and the EU guidelines along with estimates of removal by sewage treatment and receiving water dilution factors indicate that the U.S. methodology corresponds better to MEC data determined in the U.S. and Canada. Worst-case (99th centile) PECs for citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline were 30, 19, 30, 65, and 122 ng/L, respectively, using the U.S. methodology and 142, 182, 841, 144, and 575 ng/L, respectively, using the EU draft methodology. The dissipation of fluoxetine and fluvoxamine from the water column in aquatic microcosms was best described using a two-compartment model while sertraline followed a one-compartment model. Fluoxetine and fluvoxamine water concentrations initially dissipated with first phase half-lives of 3.8 and 1.8 days, respectively, but levelled off at concentrations around 10 microg/L with second phase half-lives of 76.7 and 59.3 days, respectively, not including those estimated as infinity. Sertraline dissipation tended toward the detection limit with a half-life of 3.4 days. Fluoxetine was found to be the most persistent followed by fluvoxamine and sertraline. Estimated log(K(OC)) values for all SSRIs were >4.3 indicating that SSRIs are expected to adsorb to sediment or sludge. Partitioning into other environmental compartments such as this may act as a reservoir from which SSRIs may be re-released into surface waters and indicates the potential susceptibility of benthos.

The oxidative and conjugative metabolism of sertraline was examined in vitro to identify the enzymes involved in the generation of N-desmethyl, deaminated, and N-carbamoyl-glucuronidated metabolites in humans. In human liver microsomes, sertraline was N-demethylated and deaminated by cytochrome P450 (P450) enzymes with overall K(m) values of 98 and 114 microM, respectively, but the intrinsic clearance for N-demethylation was approximately 20-fold greater than for deamination. Using P450 isoform-selective inhibitors and recombinant heterologously expressed enzymes, it was demonstrated that several P450 enzymes catalyzed sertraline N-demethylation, with CYP2B6 contributing the greatest extent, and lesser contributions from CYP2C19, CYP2C9, CYP3A4, and CYP2D6. For deamination, data supported a role for CYP3A4 and CYP2C19. Purified human monoamine oxidases A and B also catalyzed sertraline deamination with comparable K(m) values (230-270 microM). Monoamine oxidase B catalyzed the reaction approximately 3-fold faster than did monoamine oxidase A. Sertraline N-carbamoyl glucuronidation was measured in human liver microsomes in bicarbonate buffer and under a CO2 atmosphere (K(m) = 50 microM) and was catalyzed at the fastest rate by recombinant human UGT2B7. The observation that multiple enzymes appear to be involved in sertraline metabolism suggests that there should be no single agent that could substantially alter the pharmacokinetics of sertraline, nor should there be any single drug-metabolizing enzyme genetic polymorphism (e.g., CYP2D6, CYP2C19, CYP2C9, UGT1A1) that could profoundly impact the pharmacokinetics of sertraline.

Three simple and sensitive spectrophotometric methods were developed and validated for determination of the hydrochloride salts of fluoxetine, sertraline, and paroxetine in their pharmaceutical dosage forms. These methods were based on the reaction of the N-alkylvinylamine formed from the interaction of the free secondary amino group in the investigated drugs and acetaldehyde with each of 3 haloquinones, i.e., chloranil, bromanil, and 2,3-dichloronaphthoquinone, to give colored vinylamino-substituted quinones. The colored products obtained with chloranil, bromanil, and 2,3-dichloronaphthoquinone exhibit absorption maxima at 665, 655, and 580 nm, respectively. The factors affecting the reactions were studied and optimized. Under the optimum reaction conditions, linear relationships with good correlation coefficients (0.9986-0.9999) were found between the absorbances and the concentrations of the investigated drugs in the range of 4-120 microg/mL. The limits of detection for the assays ranged from 1.19 to 2.98 microg/mL. The precision values of the methods were satisfactory; the relative standard deviations were 0.56-1.24%. The proposed methods were successfully applied to the determination of the 3 drugs in pure and pharmaceutical dosage forms with good accuracy; the recoveries ranged from 99.1 to 101.3% with standard deviations of 1.15-1.92%. The results compared favorably with those of reported methods.

Sertraline is a basic compound and of pharmaceutical application for antidepressant treatment. The compound has two chiral centers. Separation of the three enantiomeric impurities from the parent compound is challenging. In this study, we successfully separated all four stereoisomers by electrokinetic chromatography using highly sulfated gamma-cyclodextrin and highly sulfated alpha-cyclodextrin as the chiral selectors. The two chiral selectors provided different selectivity and therefore affected the overall separation profiles. This may be due to the size difference between the dichlorophenyl moiety end and naphthalenamine moiety end, resulting in two different types of inclusion complexes with the different cyclodextrins. For routine analysis, highly sulfated gamma-cyclodextrin was better than highly sulfated alpha-cyclodextrin. For each stereoisomeric impurity, the method using sulfated gamma-cyclodextrin provided a limit of quantitation at or lower than 0.1% of the drug substance with adequate resolution. The critical resolution at this concentration level was not less than 4.0. Experimental data suggested that an internal standard was necessary for the purpose of quantitation, and the practical linearity range for analysis of sertraline stereoisomeric impurities was of about two orders of magnitude.

Background: The aims of the study were to quantify the drug exposure in breastfed infants of antidepressant-treated mothers, to identify possible adverse events, and to correlate these variables to maternal and infant drug metabolism-relevant genotypes and milk triglyceride content., Method: The study included 25 lactating women treated with citalopram (N = 9), sertraline (N = 6), paroxetine (N = 6), fluoxetine (N = 1), or venlafaxine (N = 3) and their 26 breastfed infants. Drug concentrations in maternal and infant serum and milk were analyzed using liquid chromotography mass spectrometry methods; milk triglyceride levels were measured with a commercial kit. Cytochrome P450 (CYP) 2D6 and CYP2C19 activity was determined by polymerase chain reaction-based genotyping of the mothers and infants. An infant adverse event questionnaire was completed by the medication-treated mothers as well as by a control group of medication-free breastfeeding mothers of 68 infants., Results: Sertraline and paroxetine were not detected in any of the drug-exposed infants. The infant serum level of citalopram was either undetectable (N = 4) or low (N = 6). All venlafaxine-exposed infants had measurable drug concentrations. We identified a paroxetine-treated mother and her infant who were both CYP2D6 poor metabolizers, as well as a citalopram-treated mother with CYP2C19 poor metabolizer status, but the serum drug levels of their infants were still either undetectable (paroxetine) or low (citalopram). There was no evidence of adverse events in the drug-exposed infants., Conclusion: Serum drug levels in breastfed infants of antidepressant-treated mothers were undetectable or low. This study adds further evidence to previously published data indicating that breastfeeding should not be generally discouraged in women using serotonin reuptake inhibitor anti-depressants.

A sensitive and stereospecific high-performance liquid chromatography (HPLC) method for determination of sertraline in bulk drug, tablets and capsules was developed. Chromatography resolution of the sertraline enantiomeric forms and trans diastereoisomers was performed on Alltima C18 (250 mm x 4.6mm i.d., 5 microm) column with hydroxypropyl-beta-cyclodextrin (HP-beta-CD) as mobile phase additive. The composition of the mobile phase was 68:32 (v/v) aqueous 170 mM phosphate buffer, pH 3.0 (adjusted with 85% phosphoric acid) containing 18 mM HP-beta-CD/acetonitrile at a flow rate of 1.0 ml x min(-1). The UV detector was set at 225 nm. Calibration curves were linear (r=0.9999, n=9) in the range of 1-120 microgml (-1) for sertraline. Limit of detection and quantitation for sertraline was 0.029 and 0.097 microg x ml (-1). The values of R.S.D. of repeatability and intermediate precision for bulk drug, tablets and capsules of sertraline hydrochloride were less than 1.0%.

Introduction: Selective serotonin reuptake inhibitors (SSRIs) are popularly prescribed for treating depression. With a few exceptions, these psychotropic medications are not approved by aeromedical regulatory authorities for use by aviators. Since SSRIs have the potential for impairing performance and causing drug-drug interactions, the prevalence of SSRIs in pilot fatalities of civil aviation accidents was evaluated., Methods: Postmortem samples from pilots involved in fatal civil aircraft accidents are submitted to the Civil Aerospace Medical Institute (CAMI) for toxicological evaluation. Findings from such evaluations are maintained in the CAMI Toxicology Database. This database was examined for the presence of SSRIs in pilot fatalities of the accidents that occurred during 1990-2001., Results: Out of 4,184 fatal civil aviation accidents from which CAMI received samples, there were 61 accidents in which pilot fatalities had SSRIs. Of these accidents, 56 were of the general aviation category, 2 were of the air taxi and commuter category, 2 were of the agricultural category, and 1 was of the ultralight category. Blood concentrations of SSRIs in the fatalities were 11-1121 ng x ml(-1) for fluoxetine; 47-13102 ng x ml(-1) for sertraline; 68-1441 ng x ml(-1) for paroxetine; and 314-462 ng x ml(-1) for citalopram. In 39 of the 61 pilots, other drugs--for example, analgesics, antihistaminics, benzodiazepines, narcotic analgesics, and/or sympathomimetics--and/or ethanol were also present. As determined by the National Transportation Safety Board, the use of an SSRI [with or without other drug(s) and/or ethanol] has been a contributory factor in at least 9 of the 61 accidents., Conclusions: Numbers of SSRI-involved accidents were low, and blood SSRI concentrations in the associated pilot fatalities ranged from subtherapeutic to toxic levels. However, the interactive effects of other drug(s), ethanol, and/or even altitude hypoxia in producing adverse effects in the pilots cannot be ruled out. Findings from this study should be useful in investigating SSRI and other substance-involved accidents and in making decisions concerning the use of SSRIs in aviation.