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Razvoj metode za merjenje vsebnosti metabolitov zdravilnih učinkovin, pogosto prisotnih v slovenskih odpadnih vodah
ID Kralj, Jan (Avtor), ID Trontelj, Jurij (Mentor) Več o mentorju... Povezava se odpre v novem oknu

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Izvleček
Ne samo izločene zdravilne učinkovine, temveč tudi njihovi metaboliti lahko predstavljajo tveganje za okolje, saj lahko s svojo ohranjeno farmakološko aktivnostjo negativno vplivajo na zdravje ljudi in drugih izpostavljenih organizmov. Zato je bil cilj magistrske naloge razviti hitro in visoko občutljivo metodo za merjenje vsebnosti izbranih metabolitov zdravilnih učinkovin, pogosto prisotnih v slovenskih odpadnih vodah. Vzorce odpadnih vod smo pripravili z metodo ekstrakcije na trdnem nosilcu s pol-avtomatskim sistemom SPE-DEX in jih analizirali z LC-MS/MS. Koncentracije analitov smo izračunali s pomočjo metode standardnega dodatka, s katero smo hkrati odpravili vpliv ozadja na točnost kvantifikacije. Metodo smo uspešno optimizirali in ovrednotili glede točnosti, ponovljivosti, delovnega območja, meje določitve, izkoristka in vpliva ozadja. Potrdili smo njeno zanesljivost in visoko občutljivost ob sočasni analizi 26 analitov (11 zdravilnih učinkovin iz več terapevtskih skupin in 15 njihovih metabolitov), ki smo jih izbrali na podlagi pregleda literature in predhodnih analiz. Metodo smo uporabili na dvanajstih realnih vzorcih odpadnih vod (treh vtočnih in devetih iztočnih), vzorčenih v devetih komunalnih čistilnih napravah iz več slovenskih regij. Od skupno 26 analitov smo jih 12 zaznali v vseh vzorcih. Če upoštevamo samo metabolite, smo jih 60 % zaznali v vseh vzorcih, 80 % pa vsaj v enem vzorcu. V največjih povprečnih koncentracijah smo v vtočnih in iztočnih vzorcih izmerili kofein (4,1 in 4,6 µg/L), 1,7-dimetilksantin (3,6 in 2,7 µg/L) in salicilno kislino (1,1 in 1,7 µg/L). Karbamazepin smo izmerili v vseh vzorcih, in sicer v povprečni koncentraciji 165,9 ng/L v vtočnih in 142,2 ng/L v iztočnih vzorcih. Diazepama, fluoksetina, norfluoksetina, paliperidona in endoksifena nismo zaznali v nobenem vzorcu. Na splošno so bile izmerjene koncentracije manjše ali primerljive z navedenimi v podobnih študijah po svetu. Za čistilne naprave, iz katerih smo dobili tako vtočni kot iztočni vzorec, smo ocenili učinkovitost odstranjevanja analitov. Koncentracije v iztočnih vzorcih so se v primerjavi z vtočnimi zmanjšale, razen pri diklofenaku in karbamazepinu, za katera smo ugotovili slabo ali celo negativno učinkovitost odstranjevanja. Predvidevamo, da izmerjene koncentracije v iztočnih vzorcih ne predstavljajo neposrednega tveganja za človeka, vseeno pa moramo v bodoče ekotoksikološke študije vključiti tudi metabolite, zlasti tiste z ohranjeno farmakološko aktivnostjo, zaradi njihovega vpliva na vodne organizme.

Jezik:Slovenski jezik
Ključne besede:metaboliti, odpadne vode, ekstrakcija na trdnem nosilcu, LC-MS/MS
Vrsta gradiva:Magistrsko delo/naloga
Organizacija:FFA - Fakulteta za farmacijo
Leto izida:2020
PID:20.500.12556/RUL-116218 Povezava se odpre v novem oknu
Datum objave v RUL:23.05.2020
Število ogledov:1108
Število prenosov:283
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Sekundarni jezik

Jezik:Angleški jezik
Naslov:Development of a method for quantification of drugs' metabolites frequently found in Slovenian wastewaters
Izvleček:
Not only eliminated pharmaceuticals, but also their metabolites may pose a risk to the environment because of their preserved pharmacological activity which may adversely affect the human health and other exposed organisms. Therefore, the aim of this Master's thesis was to develop a rapid and highly sensitive method for quantification of drugs' metabolites frequently found in Slovenian wastewaters. Wastewater samples were prepared with solid-phase extraction method using a semi-automated system SPE-DEX and analysed by LC-MS/MS. Analyte concentrations were calculated using the standard addition method, which also eliminated the influence of matrix effect on the accuracy of quantification. The method was successfully optimised and validated in terms of accuracy, precision, working range, limit of quantification, recovery and matrix effect. We confirmed its reliability and high sensitivity for the simultaneous analysis of 26 analytes (11 pharmaceuticals from multiple therapeutic groups and 15 of their metabolites), which were selected based on a literature review and preliminary analyses. The method was applied to twelve real wastewater samples (three influent and nine effluent) that were collected from nine municipal wastewater treatment plants from several Slovenian regions. Out of the total 26 analytes, 12 were detected in all samples. Considering only metabolites, 60 % were detected in all samples and 80 % in at least one sample. The highest average concentrations in influent and effluent samples were measured for caffeine (4.1 and 4.6 µg/L), 1,7-dimethylxanthine (3.6 and 2.7 µg/L) and salicylic acid (1.1 and 1.7 µg/L), respectively. Carbamazepine was measured in all samples in average concentrations of 165.9 ng/L in influent and 142.2 ng/L in effluent samples, respectively. Diazepam, fluoxetine, norfluoxetine, paliperidone and endoxifen were not detected in any sample. In general, the measured concentrations were lower or comparable to those reported in similar studies worldwide. For the wastewater treatment plants from which both influent and effluent samples were collected, the removal efficiencies of the analytes were evaluated. Concentrations in effluents decreased compared to influents, except for diclofenac and carbamazepine, which were found to have low or even negative removal efficiencies. In conclusion, the measured concentrations in effluents presumably do not pose a direct risk to humans. However, the metabolites, especially those with preserved pharmacological activity, should be included in future ecotoxicological studies due to their impact on aquatic organisms.

Ključne besede:metabolites, wastewater, solid-phase extraction, LC-MS/MS

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