How can I buy cocaine online in Petange

How can I buy cocaine online in Petange

How can I buy cocaine online in Petange

How can I buy cocaine online in Petange

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Editorial Follow us on: www. Is Luxembourg as well-connected as we thought? One of the main reasons residents cite for moving to the Grand Duchy is the connectivity it enjoys. Could that all be set to change? With the recent news that Luxair is to cut its flights to Dublin, passengers aiming to head to the UK and Ireland can only do so via a reroute and connection through London City. A trend coming to an end? With only one destination now serving the UK and Ireland London City are Expats facing taking flights from airports and airlines based abroad? Compared to the pre era where Luxair flew to Manchester, London Gatwick and London Heathrow, you could argue that British expats are left to decide between adding time to their journey pre or post, with a connection out of London City or a trip to another major airport. Even the TGV, whose initial offer price was remarkably competitive, is a darn sight cheaper if you take the train from Lorraine rather than Lux Gare. Business Review editor Stephen Evans has suggested there have been calls to make Luxembourg a low-cost hub but where would the attraction be there? Luxair have to balance the books, and the simple fact is that the dropped flights were loss-making, and it made good business sense to invest elsewhere, such as Geneva, Porto and Barcelona, but the simple fact remains, your choice of flights back home UK readers is dwindling. What are your thoughts on the matter? Send your thoughts to editorial luxmag. The evening will commence with a cocktail reception at 7 pm, followed by a sumptuous buffet dinner food and drinks are included in the ticket price. Entertainment is provided by our cultural dancers, and live music and song by New Generation. We hope you can join us in this celebration. Has a wave of creativity and inventiveness taken over their reasoning? T hen, over the weekend, 16 birds were snatched. Was the thief an animal rights activist? Or simply in search of some quick cash? The birds were stolen on Saturday from a cage outside a house in the rue V. Frommes in Diekirch. The thief stole the 16 parakeets between 2pm and 8pm, returning a few times in order to help himself. Each bird has a street value of around 50 euros. Then on Monday night, police in Remich spotted a few men walking around the vineyards with buckets filled with grapes. Trying to get out of the tricky situation, the thieves pretended to be the owners of the vineyards they had been stealing from. The first episode which aired last Sunday, 18 September is the 10th episode from season 20 and will continue from there. Repeats: Sunday 9pm, Monday 6pm and Sunday 11am. News Community Lifestyle Sport Culture Bringing the Funck back to Neudorf Dilapidated brewery to get an image overhaul N ews that the disused Henri Funck brewery in Neudorf will be turned into shops and apartments over the next few years has been met with a positive repsonse by locals of the area. In the continuation of developments for the up and coming area see Rives de Clausen , there are plans to revamp the site and turn it into a focal point for the upper part of Neudorf. The brewery ceased production in with the building slowly wearing the effects of erosion and vandalism, gradually becoming a public eyesore. Ownership of the site is maintained by Henri Funck, but the company has agreed to sell to a cast iron developer, in this case Atenor, a Belgian urban development company. Residential planning With the founding proposal initially comprising apartments, there will also be small retail outlets and the obligatory restaurants and bars, providing a boost to the local community. The news does come with a downside however: the works will require significant machinery and therefore residents can expect some delays on what is already, in terms of construction at least, a very busy stretch of road. Phantom pram pistol maidens Aparently it all happened in broad daylight, on one of the busiest roads in Luxembourg city. A man told police he was approached by two women withapramontheBoulevard Royal on Tuesday at 5pm. According to his statement, one of them suddenly pulled out a gun, and told him to go and withdraw 1, euros from a nearby bank. She then hid the gun in the pram. The man then entered the bank — under the pretext of withdrawing the money - and immediately notified the authorities. But the two women had vanished by the time police could get there. However, it all turned out to have been a false alarm: the man had apparently made it all up! I t can be downloaded or perused free of charge in English, French or German at statec. Lowestpoint:Wasserbillig,altitude m and population statistics. Did you know that, with 7, inhabitants,Kaylisthe10thmostpopulatedmunicipalityinthecountry? Or that of the , inhabitants, , are foreigners and , are women? The guide is a black and white way to see the present state of Lux. As quality goes up, so does demand. And producers are eyeing other markets for this beloved local product. The Queen Mother. T he bottle itself is remarkably commonplace:thedarkgreen colour contrasting with the wrap around, diagonal label in a much paler hue. Of course, back thenitwasoff-whitewithastylised gold sun in the top right hand corner. Now the label is gold, the sun is dark green. Some things can change in 20 years, but the bottle see p. Dirty bottle or not, the question is begged: what would the liquid inside be like? Guido shrugs. It had lost some of its sparkle, its fizz, and it tasted. Tastes have changed over time. Now it is much more everyday. The appeal has not gone down:farfromit. Infact,themyriad awards given to Moselle fizz at international festivals and fairs suggest it is getting better and more varied, while it remains very accessible. Traditionally, mainly older people, especially women, would have bought it. Now it transcends gender and age divides. Simply put, almost everyone likes it. Georges puts total production for this year at 1. Vines have been grown on the banks of the Moselle for over 2, years. Methods and technology may have changed, but few factors can have had quite the bombastic impact of this sparkling wine, which remains relatively unknown outside the Greater Region, and is positively painstaking to bring to fruition. It does, however, come from the high end of the grape spectrum: Riesling, Pinot, and the increasingly popular Auxerrois. These include clarity, bouquet and colour. And taste is also fairly important too. Even to my untrained eye, the crop this year looks bountiful. The grapes are plump and plentiful, be they Auxerrois, Rivaner, or any of the three Pinots: blanc, gris and the still very in vogue noir. Sideways was released in , but black never goes out of fashion. Wine grapes are often bitter but these ones are different. They are sweet and in excellent condition. Guido has been taking digital readings, as well as tucking into the grapes straight from the vine, and he is more than satisfied and confident about the vintage, even if it is a long way from hitting the shelves. The manufacturing process requires precision. They must also be be picked by hand. Again, this is part of the 20 year old rule that marks it apart. The Wormeldange Riesling Queenwaschosenattheweekend, and her mother is here picking grapes. This Queen Mother favours wine over G and T. Funny that. After that, they are pressed very gently to ensure the final product is never tarnished by any pips or skin. And why not? The quality to price ratio is notable and explains why it has become so popular in the domestic market as well. T heir piece and supporting documentation were chosen torepresenttheGrandDuchy of Luxembourg at the Finalist Event, hosted in Italy later this year. It encourages young students of all 27 EU countries and Norway to discuss the importance of a healthy diet, and the value of being able to make conscious choices about what we eat. An international pre-selection jury composed of journalists, communication technicians, nutritional experts, advertising agents and institutional representatives select the finalist spots from each participating country. Learn more at www. More information on NepaliMed Luxembourg a. A yckbourn is well-known for his numerous contemporary plays, which deal with adult relationships in a realistic, but very comic and enjoyable, manner. The play is about three couples whose lives are intertwined in more ways than one! All of the action takes places over a summer weekend in an English garden. Directed by Wendy Dunning-Baker. To book, you can send an email to: tickets sarumlux. By booking early, you can be assured of reserving the best seats for yourself and for your friends. Now, though, Wiltz council has finally found a private sector partner, meaning the short to mid-term future is secure. T he government left the running of the castle in the hands of the local council and stepped away from activley supporting the search for secondary investment. BrusselsBusinessInstitute,ahighereducationorganisation, have pitched in their interest and have asked to use part of the building for teaching hospitality, hotel management and catering classes. Patrons are assured that the established museums and the much-loved brasserie will remain. I was born and raised here. My fathercametolivehereinthemid-seventies. Facilitate access to decent accommodation for those in need. Esprit lift with? Chiggeri 09 DoyoufeethatLuxembourgismoney obsessed? Yes, like everywhere else. And in Luxembourg? I stopped caring about gossip. Getting to the Gare Centrale and seeing the damage caused by drugs is something that irritates me every day. Love, fear and hip-hop. Honestly, no. Sam promises to bring you the best in new and classic pop and rock music. F ans of foul language beware, next time you stub your toe, or lock yourself out of your house or watch your team concede a goal, you could find yourself in trouble, not for using such language in public but because a German drinks company has won a court battle to register the F-word as a trademark. Admittedly this probably will not affect me all that much but I do feel sorry for those in Germany who want to wear their favourite expletive covered t-shirt but now cannot. Available weekly via the App store and luxmag. Other causes of stuttering include developmental delays, neurophysiology, and extreme expectations from parentsandfamilymembers. Though there is no known instant stuttering cure, it can be overcome by being worked on continuously. This is simply ridiculous. Stuttering is similar to impaired vision or hearing speech therapy can help. Simply telling someone to stop stuttering will not do the trick. Most people who stutter do not do so because they become apprehensive, rather most people become nervous when they stutter, for fear of ridicule. News Community Lifestyle Sport Culture When stutterers sing or whisper, they may reveal no indications of impaired speech, but speaking on the telephone is the same as speaking face to face. The stuttering will still occur. J ames Cottam is a stutterer, and below he details his experiences in a funny and insightful manner, helping getting to the core of what it is like to suffer a speech impediment. Today I cycled through Pissange. I immediately thought that I must tell everybody I know about this little comedy gem, and how I would seem so clever and sophisticated for the maturity of my wit. Two thoughts struck me. The reaction from Luxembourgers would most likely be similar to a British person being told by a foreigner that they had been to Skegness — a mixture of confusion and deep, heartfelt sympathy. Now stammering is just the pinnacle of a pitiful physical and personal profile that has created numerous social challenges for me over the years. For me, the difficulties started early. At school I was always scared to raise my hand and would feign stupidity, unless I could be sure that my answer included none of the words or sounds I knew I had problems with. Presentations were dreaded months in advance leading to sleepless nights and loss of appetite. My jokes were and still are always out of place because by the time I spit it out the moment has long gone. I could therefore never have had a career in comedy. Laughter is never a good way to respond to a spluttering stutterer, but equally anticipating what I might say and finishing the sentence is a pet-hate of mine. The ability to stay and look interested or at least pretend to whilst I try to finish my sentence is the response appreciated the most — I understand that it can take forever to get my words out but believe me, it seems longer to me than to you. Now I stammer in many languages. However, when learning other languages, particularly in the early stages, you only learn one way to say a particular word or phrase and therefore substitutionofwordsbecomesimpossible. You just have to splutter your way through it as best you can. This problem was strikingly highlighted to me during a French oral exam in January where it soon became clear that I was unintelligible to the examiner because of my stammer. The frustration of knowing something but not being able to get it across is a daily annoyance for stammerers, and it sometimes manifests itself in me as aggressive outbursts. Another challenge of living in Luxembourg is that I find many of the polite words that are frequently used every day in both French and Luxembourgish have difficult starting sounds. Despite all this doom and gloom I have discovered one surprising advantage living here in a multilingual society. My slowly-increasing knowledge of French and Luxembourgish has meant that now I am now developing a choice of words in various languages. In the very near future I hope to re-start Speech Therapy in an effort to unlock new techniques to help me manage my stammer in these new situations. Rugby Club Le Far Est, in Malmedy, Belgium, were the unfortunate opposition, and with a final score of in favour of the Luxembourgers, led by captain Hamish Cullen. It is difficult to pick a single highlight of the match. However, a couple of tries stood out: one scored by Charles Xavier Ramillon, which started from a kick off, well caught by Jack Dempsey, who made a dream debut and was named Man of the Match, who took the ball up and into contact, the ball was quickly secured by the forwards, Gareth Geoffreys and Baptise Lachaise showed beautifully soft handling to get the ball to Rhys Williams, who threw a long pass, missing out Sean Ferreira, to the winger Charles-Xavier Ramillon to sprint clear and score. The other try that stood out, started in the RCL 22 meter zone, where Sean Ferreira tackled a Far Est player, the ball was secured by David Wright in the ensuing ruck, picked up Baptiste Lachaise who side stepped and weaved through the whole Far Est defence to sprint 75 meters to score. Mention also has to go to Sacha Ernstberger, omnipresent all day, who got on the score sheet when he caught a ball from the kick off, shrugged off a number of would be tacklers to score. A big thank you to the players and to SGG as sponsors. RCL are always looking for new players: please visit www. A palm-sized Panasonic robot called Evolta will be entering the mile course on 24 October, at Kona providing an interesting element to an already fiercely competitive race. Will these robots ride the TdF next year, then climb the Mt Everest? Anyway, good luck Evolta! I will see you out there on October 8th. Once upon a time, Rachel was part of a celebrated trio of secret agents who tracked down a Nazi war criminal in East Berlin in - an incident so applauded in history, that now, three decades later, her own daughter has just published a book about the exploits. For 30 years, Rachel has been living one truth, but now, as the past collides with the present, a new and deadly story begins to emerge. Cine Utopolis: Daily 2, 4. Sat also at midnight. Tue at 7. Everyone is swimming in the salt-water lake and having a blast until Malik Sinqua Walls loses his arm in what initially appears to be a tragic wake-boarding mishap. Thu 7. Sat also at quarter past midnight. News Community Lifestyle Sport cantyouseeimbusy. Though, admittedly having reread this, that sounds incredibly dull. The games are simplistic and easy to grasp and therefore utterly addictive. Plus they are designed so you can have a crafty play without being caught. No such luck. Dead Island multi-platform Zombies are niche. Not nice. The distinction is important. Shuffling Zombies are boring now, better are the rage-fuelled, faster ones. The clues in the title, see. Best not played in front of the kids. If you still give a toasted bun about what happens to Capt. Atmosphere sponges Knightly and Bloom are jettisoned as the tale attempts to become more focused. There are over 40 feature length films planned for screening and some 30 short films to be shown throughout the fortnight, including the widely acclaimed In Darkness pictured. Organised by Polska. A large photography exhibition, as well as concerts at the Atelier, the Philharmonie de Luxembourg and Exit07, are also planned. The official competition is becoming more important and prestigious, with about ten films in competition and a jury chaired by the acclaimed Polish director Agnieszka Holland. CinEast promises a lot and the organisers, speaking to LuxMag are feeling the pressure to deliver. They are confident of one thing though: there will be nothing else like this festival this year. O pen days typically take the form of fairly staid affairs. You never quite know how many numbers to expect or what stories may come about. Often eclectic can mean specific or niche and thus be seen as divisive or alienating. In the case of the open day this weekend, it means a range of workshops and performances aimed at the young and old. The opportunity to throw open the doors of these venues allows them to shed some of the artifice often lumped with an entertainment form associated with the wealthier denizen. Wonderfully simple, but a great success! Free entrance! Starts at 8pm. Tickets cost 20 euros. A booming and varied music scene presents itself through playlists and live gigs by upcoming musicians, artists or independent labels. Free entrance. From Tickets cost 12 euros. Starts at 11pm. Thursday September 22 Event Kirchberg: Play and fun is a playgroup that teaches simple Luxembourgish to non-Luxembourgish parents and their children aged approximately years. Learning through singing, actions, toys, pictures, stories and craft activities. Everyday themes such as body parts, clothes, animals, food and actions. You do not need to speak any Luxembourgish although if you do, that is great. From 9. Registrationandinfo: www. More info at www. The programme will include musical pieces by Stravinsky, Y. Braun and F. Reception after the concert. This is a free event but reservations are necessary so to reserve your seats contact agence. Tickets cost 35 euros. His music is described as a source of everything we all love: a tender, lyrical and crazily exuberant weave of colorful sounds and beautiful melodies, improvisations and ornamentation — a real embroidery of rhythms inspired by love. Starts at 7pm. Adelmo Fornaciari, better known totheworldasZuccherohasachievedworldwideacclaim since winning the Italian Castrocaro Festival in and has since then performed in front of millions of people in many countries on different continents. Doors openat6. Ticketpricesvarydepending on seats so visit www. Theprogramme will feature musical pieces by Haydn and Beethoven. Get ready for a great evening of jazz music. Tickets cost 10 euros children under 10 get in for free. For more information contact 26 51 10 38 or email :watthailux yahoo. Starts at 7. This festival is organised by Up and Down in collaboration with the Hesperange Commune. Starts at 6. As usual, there will be over young and talentedartistsshowcasingtheirtalentincludingdance, graphic design, music, fashion and more! Starts at 2. Thanks to her engaging and exuberant personality and her original lyrics, Zazie quickly made a name for herself as one of the leading female stars on the French music scene from the 90s onwards. The French pop diva has proved her songwriting talent, penning hits for not just herself but also for other major artists. The fair gives the opportunity for individuals to showcase their second-hand musical instruments for sale or exchange, and will also feature books, magazines, amps, studio recorders and other accessories and paraphernalia! There will also be live concerts and exhibitions throughout the day. Starts at 10am and finishes at 8pm. Starts at Concert is free but limited seating so get there early or reserve your seats. Also from the UK are Your Demise who will brighten up the evening with their metal-laden music that draws inspirations from bands such as Sick of it All or Hatebreed. Doors open at 7 for a 7. Tickets cost 23 euros plus presale fees. Nostalgia and rediscoveries ahead. Electronic or acoustic: a booming and varied music scene presents itself through playlists and live gigs by upcoming musicians, artists or independent labels. After learning to play the trumpet, the Berliner became one of the most talented DJs in the world and has over 15 years of experience as a composer and a live DJ. If gave his career an incredible boost, Paul Kalkbrenner now has the opportunity to show that he is and always will be the master of electronic music! His tunes always keep the clubbers in suspense. He is the undisputable master of hypnotic beats! Starts at 9pm. Tickets cost 30eurosplus presale fees. Doors open at 8pm for an 8. Tickets cost 15 euros for members or 20 euros for non-members. Like singing along to great music? This is a party where you will remember the words to almost every song!! DJ Jean Pierre will play the best music of all time! Starts at 10pm. Doors open at 8pm. Tickets cost 24 euros plus presale fees. Theresultofthisblendisawonderfullybalanced and high-quality European sonic Jazz experience. Miniimum age is 21! Presale tickets cost 12 euros and are available at Decibel bar Hollerich , Pacha bar Merl or on the Atelier website. Starts at 11am and finsihes at 4pm. Entrance fee is 5 euros. Tour, Kulturfabrik 20 Rihanna, Bercy Paris. Good condition. Suitable for Suzuki 4X4. Excellent condition. Price to discuss. If interested please phone or email luxbc hotmail. Phone Beautiful white concert-size grand piano: Excellent condition. As new with drivers and manuals EUR 2, Phone Dining Table with 6 Chairs: euros. New Designer clothing for mothers to be: Most sizes. A bargain. Phone Wood furniture for sale: Includes wardrobes, kitchen cabinets and coffee tables. Tel Kirchberg: Beautiful 2-bed apartment for rent, sqm. Hall, living, separate kitchen, bathroom, shower room, balcony, cellar, lift. Great location, wonderful views. Rent EUR 1, Three bedrooms, one with access to balcony, two bathrooms, spacious L-shaped living room, small conservatory, garage, infrared cabin, great views and large garden with sitting area. Please email: maisonstegen yahoo. Nicola Senior GaardenKarisma s. Persons advertising businesses or ads exceeding 25 words will be charged. This magazine reserves the right to remove for sale adverts after three months without notifying the person posting the advert. The English and French speaking owners will be happy to welcome you and provide the comforts to make your stay enjoyable. Includes 2 double bedrooms, sleeps 6, living, fireplace, radio, tv, canoe for use. Fishing, cycling, walking possibilities. Price EUR Mail: famplum mail. For info: www. For more information contact winn gmail. Magnificent mountain and sea views. Please call: or mail pjacobs pt. Weekend: EUR per day. Weekdays: EUR per day. Monthly: EUR per day. More information on www. Speaks French, German, Portuguese and Luxembourgish. Available from September. References provided. Tel: Handyman: seek jobs papering and scandatex painting, lay parquet, masonry. Mature Person. In Strassen. Contact michel2s pt. Please call on 4,Grand-Rue Grevenmacher Tel. Plat du jour at Lunch Time. Take Away Services. Has worked as nannybefore. He is trained as an indoor dog and is fully up to date with veterinary requirements. Whiskey is a very friendly dog who will bring a lot of happiness to his new owner as he has done in the past for our family. Please contact alanpmoran yahoo. Miscellaneous Alcoholics Anonymous: English speaking meetings Sundays Hotline or visit website www. Email: angelle. Top floor, Rue de Hollerich L, Luxembourg. Contact for more information. New arrivals in Luxembourg and women with young children are particularly welcome. Contact us on info blc. Dyspel: the support group for dyslexia and other special education needs. Meeting place is Altrimenti, 15 Ave. Consult our site for information and contacts: www. Have they taken your will, your soul, your dreams and your life? We can help. Call Cocaine Anonymous CA Luxembourg for a completely confidential conversation in English on: or visit our website www. Food and Football Sunday Live Sport all week. Snack Menu also available. Private events catered for. Dart and Pool Room. Contact us on Tel. Tel: 24 52 75 01 Having a baby? Click on www. Native American Indian club: offers Indian camping and sauna, free in Luxembourg. Contact nativamericanindianclub yahoo. Toastmasters Club Casemates Communicators: a nonprofit making organisation providing its members with the opportunity to improve their English language public speaking and presentation skills in a fun, friendly and supportive environment. Please contact John on , visit www. Professional coaching can help move your relationship forward powerfully and authentically. Business partners, couples, families and small groups are welcome. For expert advice call English or French. Are you pregnant, looking for a gentler, calmer way to give birth? Wide variety of music played. Competitive Rates. Contact sam aracityradio. Contact Samantha Schiffmann on or mail centsplaygroup yahoo. Victoria Chambers Jules does your gardening: also does painting and windowcleaning. Very competitive qrates. Tel: or email support pc-doctor. PC Doctor - for all your PC needs. FARE www. Lots of activities, fun and games. Contact Adam on for informal discussion. Weekly classes on Tuesday evening from You can also send an e-mail to lmosaic tango. Classes start the seond week of September. Contact Pastor Paul McMinimy 26 33 21 All welcome. Sunday school for children ages nursery to Contact Rev. Tim Heijermans on 36 95 83 or ath pt. Visit www. Oasis Church of God: Are you new to Luxembourg? We are a dynamic Pentecostal church in the heart of the city. Weekly home-groups. Contact Pastor Graham Kettle 81 or www. Luxembourg-Ville 47 96 1 www. Weekdays from 6 a. Sunday Entertainment show with conversation and music from 1 to 2 p. Desi Vibes Indian cultural magazine program. Sundays from 10 to Transatlantic Tunes Friday evenings from 8 to 9 p. Jump, Jive Jam Every Sunday from 6 to 7. Guillaume Schneider L Chinese 43 69 91 2 r. Van der Meulen L Danish 22 21 22 1 www. Schneider L Russian 42 23 33 r. Beggen L Luxembourg Spanish 46 02 55 4, Bld. Heinrich Heine L www. Related publications Share Embed Add to favorites Comments.

352LuxMag #125

How can I buy cocaine online in Petange

Official websites use. Share sensitive information only on official, secure websites. Pharmaceuticals and their transformation products TPs are continuously released into the aquatic environment via anthropogenic activity. To expand knowledge on the presence of pharmaceuticals and their known TPs in Luxembourgish rivers, 92 samples collected during routine monitoring events between and were investigated using nontarget analysis. Water samples were concentrated using solid-phase extraction and then analyzed using liquid chromatography coupled to a high-resolution mass spectrometer. A total of 94 pharmaceuticals, 88 confirmed at a level 1 confidence 86 of which could be quantified, two compounds too low to be quantified and six identified at level 2a, were found to be present in Luxembourg rivers. Pharmaceutical TPs 12 were also found at a level 2a confidence. Antihypertensive drugs 15 , psychoactive drugs 15 , and antimicrobials eight were the most detected groups of pharmaceuticals. A spatiotemporal analysis of the data revealed areas with higher concentrations of the pharmaceuticals, as well as differences in pharmaceutical concentrations between and The results of this work will help guide activities for improving water management in the country and set baseline data for continuous monitoring and screening efforts, as well as for further open data and software developments. Keywords: pharmaceuticals, surface water, suspect screening, HRMS, transformation products, cheminformatics, open source, nontarget screening. The geography and history of Luxembourg have distinct implications on its environment and water quality: it borders Belgium, France, and Germany, and its rivers feed into the Rhine basin. Luxembourg has vineyards lining the Moselle River, agricultural activity in the north of the country, and a population largely centered in the capital, which together brings in a significant and varied chemical load into the environment. Previous studies have reported the presence of analgesics, antimicrobials, and estrogens in Luxembourgish surface water. As there are conceivably more pharmaceuticals than the five included in targeted monitoring that enter into the environment, it is important to determine which other pharmaceuticals may be present, to gain a more holistic idea of the pharmaceutical loading in Luxembourgish surface waters. The presence of pharmaceuticals in the aquatic environment poses a threat to human and environmental health due to exposure to either the pharmaceuticals themselves or their metabolites and TPs, which may still possess bioactivity. Despite these challenges, the information that can be obtained from such analyses has a wide breadth of utility, especially for environmental studies. NTA and suspect screening are effective techniques for the monitoring and discovery of xenobiotics in the aquatic environment. MetFrag first retrieves candidates by exact mass or molecular formula from one of many available compound databases. This work focuses on the presence of pharmaceuticals and known pharmaceutical TPs present in Luxembourg surface water systems using a mixture of instrumental measurements and cheminformatics approaches. Surface water samples 1 L were collected every 4 weeks, whenever physically possible, from nine different locations in Luxembourg from April to November Figure 1 and eight different locations from April to August in in accordance with the triannual sampling strategy employed at AGE. In this strategy, four locations monitored in compliance with the WFD are consistently sampled every 4 weeks locations 1—4, Figure 1 , while the other locations throughout Luxembourg are divided into three regions and are alternately sampled during a 3 year cycle. A method blank was prepared every month to account for potential contamination from sample handling using ultrapure water. The disks were conditioned twice for 1 min using acetonitrile and then twice for 1 min using Milli-Q water. Sample loading was followed by washing the disks twice for 1 min with milli-Q water and drying by airflow for 15 min. The analytes were eluted for 1 min with cyclohexane, followed by an acetone elution for 1 min, then four times for 1 min with acetonitrile. After each elution step, the disks were air-dried for 1 min. Remaining particles were removed by passing the extracts through a 0. Sampling locations and their respective coordinates. Sampling locations 1—4 were sampled from to ; sampling locations 5—9 were sampled only in , and sampling locations 10—13 were sampled only in Mobile phases A water with 0. Lastly, the following dd settings were used: minimum AGC target 8. The instrument was calibrated and optimized every time an analysis was performed using manufacturer settings to ensure consistent performance throughout the 2 year study. Herbert Oberacher was used to monitor instrument performance between analyses. Suspect screening was performed using two suspect lists. The second suspect list consists of 82 pharmaceutical TPs. The remaining 15 TPs were obtained from Anliker et al. Detailed information on its functions, installation, and usage can be found by following the link provided above. Note that for suspect screening where t r information is not available, the t r tolerance on the MS1 level is still provided as a setting to Shinyscreen, but the whole chromatogram is screened. For suspect or target chemicals where the t r is known from previous analysis and provided in the input files , this threshold is then applied e. Features that passed QC through manual curation including peak shape, peak width, peak intensity, and alignment of the MS1 and MS2 peaks were then analyzed using MetFrag to achieve tentative identifications. Scripts used for this work are available on GitLab. Metadata were also collected for the candidates by querying the database for patent count scoring term 3 , number of PubMed references scoring term 4 , PubChem annotation count scoring term 5 , pharmacology and biochemistry information scoring term 6 , and drug and medication information scoring term 7. The latter two scoring terms assist in the interpretation of the results where multiple relevant candidates occur per mass, as described recently elsewhere, 28 as well as in the retrieval of classification information mentioned below. A more detailed explanation of the parameters used is available elsewhere. Level 1 identifications were achieved using authentic standards and the ENTACT mixtures, 43 available in-house and analyzed using the same chromatographic method used for sample analysis. Tracefinder Thermo Scientific, version 5. The concentration of pharmaceuticals in surface waters is influenced by many factors such as matrix, precipitation, volume, wastewater effluent discharge, as well as significant changes in cross-border mobility in due to the pandemic a dominating factor in Luxembourg where half of the workforce live outside the country. As a result, the spatial and temporal comparisons are limited to uncorrected concentration values here and should be interpreted accordingly. For spatial analysis, the median concentration of the identified compound across the different months was calculated and presented by sampling year. For temporal analysis, the median concentration of the identified compound across locations 1—4 was used, as these locations were sampled consistently irrespective of sampling year. A boxplot was also constructed to see which pollutants are consistently high and to show the difference in detected concentrations between and Heat maps and boxplots were generated using custom-made, openly accessible scripts in R. A simplified version of the workflow employed in this work is presented in Figure 2. After LC-HRMS analysis coupled with cheminformatics tools was performed, 88 compounds were confirmed at level 1 confidence; 86 of these could be quantified. Amantadine and 8-hydroxyquinoline concentrations were too low to be quantified. A further six compounds were identified at level 2a. These results are summarized in Tables 1 and 2. Among the detected compounds, only seven were detected in both positive and negative ionization: diclofenac, fluconazole, irbesartan, losartan, niflumic acid, oxazepam, and valsartan further identifiers are provided in the Supporting Information , Tables S1 and S2. In terms of pharmaceutical class, many of the compounds identified in this work belong to drugs for the management of heart-related diseases 15 , psychoactive drugs 15 , antimicrobials eight , and drugs for the management of pain eight. All five chemicals monitored by AGE were also detected in this study. The number of analytes, including both levels 1 and 2a, found per location in this study ranged from 23 compounds July to 52 compounds May Two TPs 3-hydroxycarbamazepine and O -desmethylvenlafaxine were identified with level 1 confidence, whereas 12 TPs were identified at level 2a confidence and are listed including their parent compounds in parentheses: 4-acetamidoantipyrine metamizole , 4-aminoantipyrine metamizole , clopidogrel carboxylic acid clopidrogel , cotinine nicotine , D verapamil , ritalinic acid methylphenydate , fenofibric acid fenofibrate , flucytosine emtricitabine , guanylurea metformin , morphine codeine , N4-acetylsulfamethoxazole sulfamethoxazole , 4-hydroxydiclofenac diclofenac. Flucytosine on its own is used as an antifungal agent, whereas morphine can be used as the parent compound for pain management. In addition, two TPs 2-hydroxycarbamazepine and 10,dihydroxycarbamazepine were tentatively identified level 3 during the parent pharmaceutical screening because they were isobaric with some parent pharmaceuticals. Note that only locations 1—4 were sampled consistently between and , in compliance with the WFD requirements; thus only data from these locations were used for the temporal analysis. Locations 5—9 were only sampled during , whereas locations 10—13 were sampled in Tables S3 negative mode and S4 positive mode in the Supporting Information summarize the individual concentration of each pharmaceutical quantified from to from each location. Median values were calculated across the concentrations measured over the relevant months of sampling for the respective compound and location. Zero-value median concentrations are indicated by gray-shaded boxes. White boxes indicate that there were no concentration values within the quantification range. All compounds were measured in positive mode except for those marked with an asterisk, which were measured in negative mode. Median values were calculated across the concentrations measured at the four permanent sampling locations for the respective compound and month—year. White boxes indicate concentration values that were below the respective quantification range, which were therefore discarded from median calculation. Among the pharmaceuticals found were antihypertensive drugs. In , sotalol and telmisartan were the antihypertensive drugs detected at the highest concentration. In contrast, irbesartan was detected to have the highest concentration during , followed by telmisartan. Clarithromycin and clindamycin, on the other hand, were the antimicrobials detected with the highest concentration in , respectively. However, in , sulfamethoxazole and trimethoprim were the highest detected antimicrobials. These drugs are known to be used together for the treatment of bacterial infections. Locations 1 and 2 consistently showed the highest concentrations of the above-mentioned antimicrobials irrespective of year. In comparison, both Alzette-Ettelbruck and Alzette-Mersch-Berschbach are downstream of the Beggen wastewater treatment plant 45 capacity: , population equivalents , which receives sewage from Luxembourg City, the biggest and most populated city in Luxembourg. Despite the bigger capacity, both sampling points are not as close to the source as the Chiers location and thus may experience dilution. Pharmaceutical compounds found in this study such as acetaminophen, caffeine, carbamazepine, clarithromycin, salicylic acid, and valsartan have been described before as markers of sewage or wastewater discharge into surface water, 46 , 47 further supporting the impact of wastewater effluents in Luxembourgish rivers. Figures 3 — 6 show the dynamic nature of pharmaceutical contamination in surface water, demonstrating that aquatic organisms in these rivers are exposed to varying mixtures over time. Since recent studies have highlighted the ecological risks associated with exposure to mixtures in surface water systems, 48 , 49 this work helps show how suspect screening may support the identification of more chemicals in surface waters and thus help improve the ecological risk assessment of mixtures in future works. Concentration values that were below the respective quantification ranges were excluded. All chemicals were measured in positive mode. The stimulant caffeine, antidepressant metabolite O -desmethylvenlafaxine, antihypertensive drugs irbesartan and telmisartan, the antidiabetic drug sitagliptin, and the opioid analgesic tramadol were among the most concentrated pharmaceuticals found in Luxembourgish surface waters Figures 3 and 4 in both and From a temporal point of view Figure 5 , the highest median concentrations of the pharmaceuticals were detected in September and October of and are consistently lower during the spring. The most visually obvious differences between the two sampling years include 1 amytriptyline, iohexol, phenylalanine, and ranitidine only detected at quantifiable levels in and 2 decreases in the median concentrations of dexpanthenol, metformin, nicotine, sotalol, and vildagliptin. As an example, metformin had median concentrations of 3. Dexpanthenol is a drug used for prophylactic purposes; both metformin and vildagliptin are drugs used for managing diabetes, sotalol is for the management of arrhythmia, while nicotine relates to smoking. A juxtaposition of data from and is presented as boxplots in Figure 6 , showing the general decrease in many pharmaceutical concentrations in green boxes. For simplicity, only the top 50 pharmaceuticals ranked by median concentration are presented. Some of the most notable drops in detected concentration were observed for dexpanthenol, nicotine, metformin, and sotalol. The individual concentrations of the analytes per sampling location and time are summarized in Tables S3 and S4 in the Supporting Information. Interestingly, lower median concentrations of the pharmaceuticals were measured in compared to those measured in as shown in Figure 6 , which may be partially due to the reduced presence of cross-border workers during the pandemic. COVID has brought on a major shift in working practices, as more people were advised and allowed to work remotely. In Luxembourg, a major part of the workforce comprises cross-border workers approximately , people in Two interesting features in Figure 6 , also apparent in Figure 5 , are the detections of iohexol and ranitidine in but not in Iohexol is a radiocontrast agent used for medical imaging. Due to the COVID pandemic, there was a significant decrease in medical procedures for noncommunicable diseases, including radio imaging. Ranitidine use in the EU, on the other hand, was discontinued in because of the suspected carcinogen N -nitrosodimethylamine, an impurity present in ranitidine drugs. Changes in precipitation had been reported to affect contaminant levels in water, generally increasing with increased precipitation due to factors such as runoff and combined sewer overflow. For the samplings months that were studied in both and April, May, July, and August , showed the lowest amount of precipitation, which may have contributed to the lower concentration of pharmaceuticals detected. While there was not sufficient data available in this study to fully account for all factors influencing the concentration such as population, precipitation, matrix effects, and extraction recoveries, these results reveal interesting trends that will be the subject of further work. While the Chiers flows into the Meuse River and the Alzette flows into the Sauer River eventually leading into the Rhine , both rivers contribute to the chemical load that eventually ends up in the North Sea. Several studies have determined the presence of pharmaceuticals in the Meuse and Rhine rivers. A study by ter Laak et al. Despite being apart by almost a decade, similar trends can be observed in Luxembourgish waters. Later studies of different parts of the Rhine and Meuse rivers reported similar pharmaceuticals; 55 , 56 however, in some studies, the antidiabetic drug metformin and its TP guanylurea were found to be the most abundant pharmaceutical in surface water samples. Higher levels of the antidiabetic drug sitagliptin, fifth most abundant, were detected in Luxembourg. The two drugs differ in their mode of regulating sugar in the body. The presence of isobars, isomers, and in-source fragments complicates the identification of chemicals in HRMS data, sometimes even leading to these analytes to be excluded from HRMS analysis. While cases a—d were easily resolved using authentic standards, cases e and f introduced specific challenges. Using standards, the first peak In order to quantify both compounds, the peaks had to be manually integrated to avoid integrating the two peaks as one compound. For the suspect screening of phenytoin, three prominent peaks t r : Looking at the structure of phenytoin, the absence of chiral carbons renders the possibility of diastereomers, which could explain the presence of multiple peaks, invalid. Analysis of the phenytoin standard showed that this compound elutes at Further inspection using MetFrag and database matching suggested that the second and third peaks belong to the positional isomers 2-hydroxycarbamazepine and 3-hydroxycarbamazepine, metabolites of the anticonvulsant carbamazepine. The t r matching using a standard confirmed that the peak at However, the first and biggest peak proved to be challenging. Inspection of the MS1 spectrum at Using these pieces of information, it can be suggested that the Using The presence of the B MS1 spectrum of the E MS2 spectrum of the phenytoin standard structure on the same pane. One case that needs further inspection is the stereoisomers vidarabine and adenosine, which are impossible to separate using the chromatographic method employed in this study. While there are reports on the utility of ion mobility to discriminate between stereoisomers, it is still to be tested whether such resolution is practically achievable. This study documents suspect screening efforts thus far for pharmaceuticals and their known TPs as a starting point for further understanding pharmaceutical levels in Luxembourgish surface waters. Other activities looking into different chemical classes such as pesticides, 66 industrial chemicals, and other emerging pollutants are ongoing. The continuous analysis of surface water using HRMS as part of the routine monitoring efforts will enable retrospective screening 67 , 68 for newly identified contaminants that may impact local surface water quality and biota, such as the effect observed by city runoff on coho salmon. Other tentative identifications have been communicated with AGE, and these, along with more detailed trend analysis as more temporal data points are collected, can be investigated in future works as resources allow. Quantification efforts could be further improved using the list of pharmaceuticals identified in this work as a target list, as well as investing in isotopically labeled standards which was beyond the scope of the current works, as target analysis is performed by AGE. Finally, as experimental databases increase in size and coverage, the ability to screen for more compounds with higher confidence with these open source methods such as the one presented here will also increase, highlighting the need for the community at large to continue to contribute to publicly available databases. One main factor limiting TP suspect screening is the lack of available information in open databases that is standardized and thus suitable to be extracted consistently and reproducibly to form meaningful suspect lists. The authors acknowledge the people in the background who tirelessly collect samples and have contributed to this work through healthy discussions in the office, as well as all those contributing to the many open science efforts mentioned. The data as. All other code and databases used as part of MetFrag identification are likewise openly available links inline throughout this article. Tables of CNS suspects, pharma IDs, negative mode, positive mode, positive concentration, and the original file names and their corresponding names in this paper the original file names were kept to allow traceability to the original sample files stored locally at the University of Luxembourg XLSX. All authors revised and approved the submitted version. This section collects any data citations, data availability statements, or supplementary materials included in this article. As a library, NLM provides access to scientific literature. ACS Environ Au. Find articles by Randolph R Singh. Find articles by Adelene Lai. Find articles by Jessy Krier. Find articles by Philippe Diderich. Find articles by Emma L Schymanski. Collection date Nov Published by American Chemical Society. Open in a new tab. Similar articles. Add to Collections. Create a new collection. Add to an existing collection. Choose a collection Unable to load your collection due to an error Please try again. Add Cancel.

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