Mass balance, metabolic disposition, and pharmacokinetics of [14C]ensartinib, a novel potent anaplastic lymphoma kinase (ALK) inhibitor, in healthy subjects following oral administration.

PURPOSE: Ensartinib is a novel, potent and highly selective inhibitor of anaplastic lymphoma kinase (ALK) that has promising clinical activity and low toxicity in patients with ALK-positive non-small cell lung cancer. This study was conducted to investigate the pharmacokinetics, metabolism and excretion of ensartinib following a single 200 mg/100 µCi oral dose of radiolabeled ensartinib to healthy subjects. METHODS: Six healthy male subjects were enrolled and administrated an oral suspension in a fasted state. Blood, urine and feces were collected. Radioactivity concentrations were measured by liquid scintillation counting and plasma concentrations of ensartinib by liquid chromatography-tandem mass spectrometry. Both techniques were applied for metabolite profiling and characterization. RESULTS: The mean total recovery was 101.21% of the radiolabeled dose with 91.00% and 10.21% excreted in feces and urine, respectively. Unchanged ensartinib was the predominant drug-related component in urine and feces, representing 4.39% and 38.12% of the administered dose, respectively. Unchanged ensartinib and its metabolite M465 were the major circulating components, accounting for the same 27.45% of the plasma total radioactivity (AUC0-24h pool), while other circulating metabolites were minor, accounting for less than 10%. Mean Cmax, AUC0-∞, T1/2 and Tmax values for ensartinib in plasma were 185 ng/mL, 3827 h ng/mL, 18.3 h and 3.25 h, respectively. The total radioactivity in plasma was cleared with terminal half-life of 27.2 h. Treatment with ensartinib was well tolerated, and no serious adverse events were reported. CONCLUSION: It was well tolerated in the six healthy male subjects following a single oral administration of 200 mg/100 µCi dose of ensartinib. Besides unchanged ensartinib, metabolite of M465 was the predominant circulating drug-related component. The drug was primarily eliminated in feces. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03804541.

Determination, risk assessment and processing factors for pyridaben in field-incurred kiwifruit samples.

Field trials in six agricultural sites were carried out to investigate the dissipation and residue levels of pyridaben in kiwifruit. Each sample was extracted with acetonitrile, purified with octadecylsilane and analyzed with high-performance liquid chromatography-tandem mass spectrometry. The method had good linearity (R2 > 0.99), accuracy (recoveries of 78.53-98.00%) and precision (relative standard deviation of 0.86-6.11%). The dissipation of pyrdaben in kiwifruit followed first-order kinetics with a half-life < 8 d, and terminal residues in kiwifruit were lower than 0.5 mg/kg after 14 d of application. Risk assessment indicated that both chronic and acute dietary intake risk values were far below 100%, suggesting that pyridaben residues in kiwifruit were relatively safe to humans. Moreover, the effects of traditional household processes on kiwifruit were investigated. The processing factors (PFs) indicated that peeling and peeling-juicing processes could remove pyridaben residues from kiwifruit, and the former was more effective than the latter (PF at 0.15 vs. 0.51). Nevertheless, drying kiwifruit with an oven increased the amount of pyridaben (PF at 1.05). These results could provide guidance for the safe and reasonable use of pyridaben in agriculture and may be helpful for the Chinese government to determine maximum residue limit of pyridaben in kiwifruit.

Drug Distribution in Living Cells via Label-Free Molecular Fingerprint.

A new application of stimulated Raman scattering (SRS) uses the benefit of a label-free molecular fingerprint to image the uptake and distribution of an alkyne-based drug in living cells. This method delivers information on cellular molecular composition and drug-cell interaction, showing the potential of SRS in drug development.

In vitro metabolites characterization of ponatinib in human liver microsomes using ultra-high performance liquid chromatography combined with Q-Exactive-Orbitrap tandem mass spectrometry.

Ponatinib is an oral drug for the treatment of chronic myeloid leukemia and acute lymphoblastic leukemia, which has been reported to increase the risk of hepatotoxicity. The aim of this study was to characterize the metabolites of ponatinib in human liver microsomes as well as its reactive metabolites. Ponatinib was incubated with human liver microsomes in the presence of NADPH and trapping agents (glutathione or potassium cyanide). The metabolites were characterized by liquid chromatography in combination with Q-Exactive-Orbitrap-MS. Under the current conditions, six metabolites were detected and structurally identified on the basis of their accurate masses, fragmentation patterns, and retention times. M3 (N-demethylation) was unambiguously identified by matching its retention time and fragment ions with those of its reference standard. N-demethylation and oxygenation were proved to be the predominant metabolic pathways of ponatinib. In addition, two reactive metabolites (cyano adducts) were detected in human liver microsomes in the presence of potassium cyanide and NADPH, suggesting that ponatinib underwent CYP450-mediated metabolic activation, which could be one of the causative mechanisms for its hepatotoxicity. The current study provides new information regarding the metabolic profiles of ponatinib and would be helpful in understanding the effectiveness and toxicity of ponatinib, especially the mechanism of hepatotoxicity.

Residues and dissipation kinetic of abamectin, chlorfenapyr and pyridaben acaricides in green beans (Phaseolus vulgaris L.) under field conditions using QuEChERS method and HPLC.

The current study estimated the dissipation rates of abamectin, chlorfenapyr and pyridaben acaricides in pods of green beans (Phaseolus vulgaris L.) under field conditions in Egypt. Pesticides were extracted and cleaned-up by QuEChERS method and were analyzed by HPLC. The dissipation of these acaricides followed the first order kinetics model with half-life (t1/2) values 1.00, 3.50 and 1.50 days for abamectin, chlorfenapyr and pyridaben, respectively. The lowest residues, at different time intervals of field application rate of each pesticide, were observed with abamectin followed by pyridaben and then chlorfenapyr. Pre-harvest intervals (PHIs) were 10.00, 13.50 and 6.00 days for abamectin, chlorfenapyr and pyridaben, respectively and were below the established European maximum residue limits (EU MRLs) 10-14, 14-21 and 7-10 days after application, respectively. If the fresh pods will be consumed after harvest, it is expected that the presence of these pesticides in the food will have a negative impact on human health. Therefore, the elimination of the residues of these harmful pesticides must be carried out.

Ambrisentan use in a HIV-1 infected patient with end-stage renal disease and pulmonary hypertension: minimal removal by hemodialysis - a case report.

BACKGROUND: Ambrisentan is a selective endothelin receptor antagonist used for the treatment of pulmonary arterial hypertension (PAH). Little is known about ambrisentan removal by hemodialysis in patients with end-stage renal disease (ESRD). CASE PRESENTATION: A 53-year-old woman with HIV/hepatitis C virus (HCV) co-infection, PAH and ESRD on regular hemodialyis was admitted in our hospital due to refractory heart failure while on treatment with bosentan (125 mg twice daily) and tadalafil (20 mg once daily) for PAH and antiretroviral treatment (cART) including darunavir/cobicistat (800/150 mg once daily). Excessive exposure to bosentan due to drug interactions between bosentan and darunavir/cobicistat was suspected. Bosentan was replaced by ambrisentan, with progressive improvement in her clinical condition. Pre- and postdialyzer cocentrations of ambrisentan in plasma were determined and hemodialysis extraction ratio for ambrisentan was 2%. CONCLUSIONS: Our results suggest that hemodialysis results in minimal ambrisentan removal, and therefore no specific ambrisentan dosage adjustment seems to be required in ESRD patients undergoing hemodialysis.

Determination and Modeling on Ultraviolet Light Degradation of Pyridaben Based on Fluorescence Spectrum.

AIMS AND OBJECTIVE: Pesticide residues seriously affect human health, so it is very important to study the degradation of pesticide residues for food safety. The degradation of pyridaben by ultraviolet (UV) irradiation was studied, the degradation characteristics and modeling were analyzed in this paper. This study was undertaken to fully reveal the degradation mechanism of UV irradiation for pyridaben residue and provided the evaluation method of degradation effect. MATERIALS AND METHODS: Firstly, the fluorescence spectra of pyridaben samples were measured by LS55 fluorescence photometer, and the relationship between pyridaben concentration and the fluorescence intensity of characteristic peak was established. Then, using UV irradiation approach, the pyridaben was degraded to different degrees by controlling the irradiation time. The degradation process was characterized according to the change of fluorescence characteristic peak intensity before and after degradation. The relationship between degradation time and fluorescence intensity was established at last. RESULTS: The results showed that the fluorescence characteristic peak of pyridaben was located at 356 nm. The pyridaben content prediction model function was obtained with the correlation coefficient of 0.9989 and the average recovery of 99.70%. The relative standard deviation (RSD%), the limit of detection (LOD) and the limit of quantity (LOQ) was 1.71%, 0.0058 ug/ml and 0.0193 ug/ml, respectively. The exponential function model between UV degradation time and fluorescence intensity was obtained, the corresponding correlation coefficient was 0.9991, and the average recovery was 100.49%. CONCLUSION: UV light irradiation can effectively degrade pyridaben, degradation process can be characterized by the change of fluorescence intensity, and the degradation model was tested to be accurate.

Utilizing Stimulated Raman Scattering Microscopy To Study Intracellular Distribution of Label-Free Ponatinib in Live Cells.

Stimulated Raman scattering (SRS) microscopy represents a powerful method for imaging label-free drug distribution with high resolution. SRS was applied to image label-free ponatinib with high sensitivity and specificity in live human chronic myeloid leukemia (CML) cell lines. This was achieved at biologically relevant, nanomolar concentrations, allowing determination of ponatinib uptake and sequestration into lysosomes during the development of acquired drug resistance and an improved understanding of target engagement.

Enhancement of tripartite synapses as a potential therapeutic strategy for Alzheimer's disease: a preclinical study in rTg4510 mice.

BACKGROUND: The lack of effective treatment options for Alzheimer's disease (AD) is of momentous societal concern. Synaptic loss is the hallmark of AD that correlates best with impaired memory and occurs early in the disease process, before the onset of clinical symptoms. We have developed a small-molecule, pyridazine-based series that enhances the structure and function of both the glial processes and the synaptic boutons that form the tripartite synapse. Previously, we have shown that these pyridazine derivatives exhibit profound efficacy in an amyloid precursor protein AD model. Here, we evaluated the efficacy of an advanced compound, LDN/OSU-0215111, in rTg4510 mice-an aggressive tauopathy model. METHODS: rTg4510 mice were treated orally with vehicle or LDN/OSU-0215111 (10 mg/kg) daily from the early symptomatic stage (2 months old) to moderate (4 months old) and severe (8 months old) disease stages. At each time point, mice were subjected to a battery of behavioral tests to assess the activity levels and cognition. Also, tissue collections were performed on a subset of mice to analyze the tripartite synaptic changes, neurodegeneration, gliosis, and tau phosphorylation as assessed by immunohistochemistry and Western blotting. At 8 months of age, a subset of rTg4510 mice treated with compound was switched to vehicle treatment and analyzed behaviorally and biochemically 30 days after treatment cessation. RESULTS: At both the moderate and severe disease stages, compound treatment normalized cognition and behavior as well as reduced synaptic loss, neurodegeneration, tau hyperphosporylation, and neuroinflammation. Importantly, after 30 days of treatment cessation, the benefits of compound treatment were sustained, indicating disease modification. We also found that compound treatment rapidly and robustly reduced tau hyperphosphorylation/deposition possibly via the inhibition of GSK3ß. CONCLUSIONS: The results show that LDN/OSU-0215111 provides benefits for multiple aspects of tauopathy-dependent pathology found in Alzheimer's disease including tripartite synapse normalization and reduction of toxic tau burden, which, in turn, likely accounted for normalized cognition and activity levels in compound-treated rTg4510 mice. This study, in combination with our previous work regarding the benefit of pyridazine derivatives against amyloid-dependent pathology, strongly supports pyridazine derivatives as a viable, clinically relevant, and disease-modifying treatment for many of the facets of Alzheimer's disease.

Residue, dissipation, and safety evaluation of etoxazole and pyridaben in Goji berry under open-field conditions in the China's Qinghai-Tibet Plateau.

The dissipation and residual levels of etoxazole and pyridaben in Goji berry under open field conditions were determined by using GC-NPD (gas chromatography with nitrogen and phosphorus detector) with modified QuEChERS method. At fortification levels of 0.01, 1, and 5 mg/kg in Goji berry, it was shown that recoveries were ranged from 80.40 to 100.9% with relative standard deviation of the method (RSD) for repeatability ranged from 2.20 to 4.25%. The limit of quantification (LOQ) of the method was 0.01 mg/kg. The dissipation rates of etoxazole and pyridaben were described by using first-order kinetics and its half-life, as they are 7.13 days, 5.77 days, and 5.99 days (etoxazole) and 1.02 day, 0.67 day, 1.02 day (pyridaben). The terminal residues of etoxazole and pyridaben were below the European maximum residue limit (MRL, 0.1 mg/kg) in Goji berry when measured 7 days after the final application, which suggested that the use of these insecticides was safe for humans. This study would help in providing the basic information for developing regulation to guard a safe use of etoxazole and pyridaben in Goji berry and prevent health problem from consumers.

Microbial transformation of ambrisentan to its glycosides by Cunninghamella elegans.

The purpose of this paper is to describe the glycosylation of ambrisentan (AMB) by cultures of Cunninghamella elegans ATCC 9245. AMB is an endothelin receptor antagonist, which is used to treat pulmonary arterial hypertension. Filamentous fungi are morphologically complex and may exhibit different forms depending on the species and the nature of the culture medium. A biotransformation study was conducted to investigate the ability of C. elegans to metabolize AMB. Parameters were optimized by testing on different culture media and concentrations, pH, drug concentration, static and shaking conditions. Ambrisentan's metabolite, obtained after 240 h of incubation as a result of glycosylation pathway, was separated by HPLC and determined by high-resolution mass spectrometry. The method showed linearity over 300-1000 µg mL-1 (r = 0.998). Accuracy, precision, robustness and stability studies agree with international guidelines. Results are consistent in accordance with the principles of green chemistry as the experimental conditions had a low environmental impact, and used little solvent.

Isolation, identification, characterization, synthesis and quality control strategy of new process-related impurities in ambrisentan.

Ambrisentan is a highly selective endothelin-A receptor antagonist for the treatment of pulmonary arterial hypertension (PAH). The analysis of the process-related impurities will help not only to optimize the process parameters but also to develop reasonable analytical methods and set the quality standard for a quality control strategy in pharmaceutical manufacturing. During the manufacture of ambrisentan, five unknown impurities were detected in pilot batches ranging from 0.05% to 0.15% by HPLC. All of these impurities were isolated and synthesized successfully and were identified and characterized by LC-MS, HRMS, ESI-MS/MS(Q-Tof), 1D-NMR (1H, 13C, DEPT) and 2D-NMR (COSY, HSQC, HMBC) techniques. The formation mechanisms that yield these impurities are discussed for the first time. Quality control strategies to deal with these impurities are developed to obtain bulk drug of ICH-grade quality.

LC-ESI-MS/MS identification and characterization of ponatinib in vivo phase I and phase II metabolites.

Ponatinib (Iclusig®) is a multi-targeted tyrosine kinase inhibitor (TKIs). It is active against T315I and other BCR-ABL mutants. Investigation of in vivo metabolism of ponatinib was done using Sprague Dawley rats by giving one oral dose of PNT (4.7 mg/kg) to each rat and urine samples were gathered at several time intervals from dosing. Filteration of urine samples was done through 0.45 µm syringe filters. Phase separation using ACN was applied for extraction of ponatinib related metabolites. Characterization and identification of one in vivo phase II metabolite and thirteen in vivo phase I of PNT were done using LC-MS/MS. Phase I metabolic reactions were reduction, N-demethylation, hydroxylation, N-oxidation, oxidation and amide hydrolysis. Phase II metabolic reaction was glucuronidation of hydroxyl benzyl metabolites of ponatinib. The major in vivo metabolic reactions were α hydroxylation and α oxidation at piperazine ring. Literature review revealed no articles that have been published on in vivo metabolism of ponatinib in Sprague Dawley rats or ponatinib in vivo phase I and phase II metabolites structural characterization and identification.

Simultaneous determination of pyridaben, dinotefuran, DN and UF in eggplant ecosystem under open-field conditions: Dissipation behaviour and residue distribution.

A sensitive method for simultaneous determination of pyridaben, dinotefuran, DN and UF in eggplant ecosystem was established and validated through rapid resolution liquid chromatography triples quadrupole tandem mass spectrometry (RRLC-QqQ-MS/MS). Matrix-matched external calibrations were introduced to check matrix effects. Limits of quantification (LOQs) of pyridaben, dinotefuran, DN and UF in eggplant were 0.2, 0.2, 1.0 and 1.0 µg kg-1, and 0.2, 0.2, 5.0 and 1.0 µg kg-1 in soil, respectively. Limits of detection (LODs) of four pesticides were below 0.41 µg L-1. The mean recoveries (n = 5) of these insecticides varied from 79.4% to 103%, and the relative standard deviations (RSDs) ranged from 2.1% to 15.3% at three levels. This method was applied to Chinese open-field samples from two representative locations, which were previously treated with these insecticides at the doses of 210-315 g a.i. ha-1 twice or three times. The dissipations of pyridaben and dinotefuran in eggplant and soil followed first-order kinetics with the half-lives of 3.65-11.4 d. The residues of pyridaben and total dinotefuran (calculated as sum of dinotefuran parent, DN and UF) in eggplant were below 0.0311 mg kg-1 at the pre-harvest interval (PHI, 7 d). Presently, no maximum residue limit (MRL) of pyridaben and dinotefuran in eggplant was recommended by China, Codex Alimentarius Commission (CAC) or European Union (EU). This study was important for evaluation of environmental fate and food safety of pyridaben and dinotefuran in eggplant ecosystems, and facilitated China to establish maximum residue limits (MRLs) of pyridaben and dinotefuran in eggplant.

Studies on new substituted pyridazinones: synthesis and biological evaluation

We report herein the synthesis and pharmacological evaluation of a new series of 6-aryl-2-(imidazol-1-yl/1,2,4-triazol-1-yl)-2-methyl-4,5-dihydro-(2H)-pyridazin-3-one (3a-j) as potential anticonvulsant and antitubercular agents. The title compounds were prepared by reacting 6-aryl-4,5-dihydro-(2H)-pyridazin-3-one (2a-e) with formaldehyde and secondary cyclic amine imidazole or 1,2,4-triazole as per Mannich reaction. Anticonvulsant activity of pyridazinone derivatives was tested at 50 mg.kg-1 dose level against maximal electroshock (MES), isoniazid (INH, 250 mg.kg-1) and pentylenetetrazole (PTZ at 80 mg.kg-1) induced seizure methods. Phenytoin sodium (25 mg.kg-1) and sodium valproate (100 mg.kg-1) were used as reference drugs for comparison purpose. In-vitro antitubercular activity was tested by Microplate Alamar Blue assay (MABA) method and the results were compared with clinically used antitubercular agents such as INH, Pyrazinamide (PZA) and Streptomycin (STM). None of the screened compounds were found to be neurotoxic at a dose level of 100 mg.kg-1. All the screened compounds (3a-j) significantly reduced the MES, INH and PTZ induced convulsions and thus showed good anticonvulsant activity. The minimum inhibitory concentration (MIC) of the title compounds against M. tuberculosis ranged from 1.6 µg/mL to 6.25 µg/mL in comparison to INH, PZA (3.125 µg/mL) and STM (6.25 µg/mL) which indicated good antitubercular activity.

Evaluation of Pyridaben Residues on Fruit Surfaces and Their Stability by a Novel On-Line Dual-Frequency Ultrasonic Device and Chemiluminescence Detection.

In this paper, we first report the development of a highly sensitive and economical method for accurate analysis of pyridaben residues on fruits based on dual-frequency ultrasonic treatment (DFUT) and flow injection chemiluminescence (CL) detection. The DFUT device is made by integrating an ultrasonic bath with an ultrasonic probe. Two quartz glass coils (QGC) with different structures have been designed and applied to evaluate the function of DFUT in the detection process. Recorded data showed that DFUT is an effective method for improving the pyridaben CL signal. The signal of pyridaben in response to DFUT is 2.0-3.3 times stronger than the response to only the ultrasonic probe at 20 kHz or the ultrasonic bath at 40 kHz. In addition, the response obtained from the concentric circle QGC is 2.1 times stronger than the response to the spiral tube QGC. Under the optimized condition, the proposed method has advantages, such as a wide linear range (0.8-100.0 µg L-1), a high sensitivity (limit of detection of 0.085 µg L-1), and good stability (RSDs ≤ 4.7% in the linear range) for pyridaben determination. We apply this method to monitor the residue pyridaben on some fruits. The data show that the maximum amounts of the residue on fruit surfaces after soaking in water (50 mg L-1, 5 min) are 0.583 mg kg-1 (apple), 0.794 mg kg-1 (orange), and 0.351 mg kg-1 (pear). However, the concentration of pyridaben in the presence of sunlight decreases rapidly, showing its poor light stability.

Determination of norflurazon concentration in wheat leaves using a modified QuEChERS method.

The aim of this analytical study was to develop and validate an easy-to-use method for measuring the actual level of norflurazon that accumulates in leaves. We amended the QuEChERS method, i.e. Quick, Easy, Cheap, Effective, Rugged, and Safe, which is widely used for pesticide and herbicide analysis in food, and usually combined with HPLC-MS detection. We adapted this method for the detection of norflurazon in leaves or leaf fragments and proposed a useful modification using of HPLC-UV detection. Reproducible retention times of 3.11±0.04 min, precision (RSD<8.0%), LOQ=315 ng∙mL-1 and linearity (R=0.99874) were achieved.

Chromatographic Study of Azintamide in Bulk Powder and in Pharmaceutical Formulation in the Presence of Its Degradation Form.

Two specific, sensitive, and precise stability-indicating chromatographic methods were developed, optimized, and validated for the determination of Azintamide (AZ) in the presence of its degradation product. The first method was TLC combined with the densitometric determination of the separated bands. Separation was achieved using silica gel 60 F254 TLC plates and chloroform-acetone-glacial acetic acid (7.5 + 2.1 + 0.4, v/v/v) as the developing system. Good correlations were obtained between the integrated peak area of the studied drug and its corresponding concentrations in the linearity range. The second method used HPLC with UV diode-array detection, in which the proposed method was applied for the quantitative determination of AZ in the presence of its acidic degradation product and the quantitative determination of the acid-induced degradation product of AZ (AZ Deg) using pentoxifylline as the internal standard. The proposed components were separated on a reversed-phase C18 analytical column using acetonitrile-water (50 + 50, v/v). The flow rate was maintained at 0.55 mL/min and the detection wavelength was 260 nm. Linear regressions were obtained in the range of 1-30 and 0.3-16 µg/mL for AZ and AZ Deg, respectively. Different parameters affecting the suggested methods were optimized for maximum separation of the cited components. The suggested methods were validated in compliance with the International Conference on Harmonization guidelines and successfully applied for the determination of AZ in its pure powder form and in its pharmaceutical formulation. Both methods were also statistically compared with the reported method with no significant difference in performance observed.

Dual time-point imaging for post-dose binding potential estimation applied to a [11C]raclopride PET dose occupancy study.

Receptor occupancy studies performed with PET often require time-consuming dynamic imaging for baseline and post-dose scans. Shorter protocol approximations based on standard uptake value ratios have been proposed. However, such methods depend on the time-point chosen for the quantification and often lead to overestimation and bias. The aim of this study was to develop a shorter protocol for the quantification of post-dose scans using a dual time-point approximation, which employs kinetic parameters from the baseline scan. Dual time-point was evaluated for a [11C]raclopride PET dose occupancy study with the D2 antagonist JNJ-37822681, obtaining estimates for binding potential and receptor occupancy. Results were compared to standard simplified reference tissue model and standard uptake value ratios-based estimates. Linear regression and Bland-Altman analysis demonstrated excellent correlation and agreement between dual time-point and the standard simplified reference tissue model approach. Moreover, the stability of dual time-point-based estimates is shown to be independent of the time-point chosen for quantification. Therefore, a dual time-point imaging protocol can be applied to post-dose [11C]raclopride PET scans, resulting in a significant reduction in total acquisition time while maintaining accuracy in the quantification of both the binding potential and the receptor occupancy.

Methods comparison, transport and distribution of polar herbicides in the Baltic Sea.

Two LC-MS/MS methods including different sample preparation and quantitative processes showed a good agreement for analysis of the herbicides MCPA, mecoprop, isoproturon, bentazon and chloridazon, and the metabolite chloridazon-methyl-desphenyl (CMD) in estuarine waters. Due to different sensitivity of the methods only one could be used to analyze marine samples. The transport of these compounds to the Baltic Sea via ten German estuaries and their distribution between coastal water and sediments was studied. The results showed that all selected compounds can be transported to the Baltic Sea (0.9-747ng/L). Chloridazon, bentazon, isoproturon and CMD were detected (0.9-8.9ng/L) in the coastal waters and chloridazon and isorproturon in the sediments (5-136pg/g d.w.). Levels of contaminants in the sediments could be influenced by the total organic carbon content. Concentrations observed in the Baltic Sea are most likely not high enough to cause acute effects, but long term effect studies are strongly recommended.