Present Ph.D. Thesis is focused on the development of electrochemical methods for determination of anticancer drugs using various types of membranes for their preliminary separation. Furthermore, this Thesis reports the study of transport mechanisms of heavy metals in the presence of phytochelatins across biological membranes. Sodium anthraquinone-2-sulphonate (AQS) was used as a model compound for its similar structure with anthraquinone-based (AQ-based) anticancer drugs (doxo/daunorubicin) and also due to its better availability. All these compounds can be easily electrochemically oxidized and/or reduced. Redox behaviour of AQS was investigated by cyclic voltammetry (CV) and differential pulse voltammetry (DPV) in a cathodic region on mercury meniscus modified (m-AgSAE) and polished silver solid amalgam (p-AgSAE) electrodes, Obtained results were used for the development of a micro-volume voltammetric cell (MVVC). Its applicability for voltammetric determination of anticancer drugs was verified by using doxorubicin (DX) as a model substance. The second part of this Thesis deals with therapeutic monitoring of anticancer drugs in the blood circulation of the patients. For pilot experiments, a liquid-flow system with dialysis catheter and amperometric detection was used. The flow rate of carrier...

<p>Danas, u raznim analitičkim laboratorijama postoji veći broj analitičkih protokola,<br />zasnovanih bilo na izuzetno sofisticiranim ili jednostavnijim tehnikama, koji služe za<br />određivanje različitih ciljnih analita od farmakolo&scaron;kog značaja. Među tim grupama ciljnih analita pripadaju i antibiotici koji predstavljaju veliko otkriće u oblasti medicine i zahvaljujući njima spa&scaron;eno je vi&scaron;e od sedam miliona života, ali pored navedenih koristi, antibiotici mogu da izazovu&nbsp; veliki broj neželjenih efekata i žučne kiseline zajedno sa svojim derivatima, koji su fiziolo&scaron;ki deterdženti, mogu biti citotoksične za organizam ako se njihova koncentracija ne kontroli&scaron;e. U ovoj doktorskoj disertaciji prikazan je razvoj analitičkih metoda pre svega voltametrijskihmetoda u kombinaciji sa jednostavnim i savremenim elektrodama/senzorima za određivanje&nbsp; odabranih analita kao &scaron;to je antraciklični antibiotik doksorubicin (DOX), makrolidni antibiotici<br />eritromicin-etilsukcinata (EES), azitromicina (AZI), klaritromicina (CLA) i roksitromicina&nbsp; (ROX) i 3-dehidro-deoksiholne kiseline.</p><p>Voltametrijska karakterizacija i određivanje gore navedenih antibiotika primenom obnovljive srebro-amalgam film elektrode (Hg(Ag)FE)rađena je direktnom katodnom&nbsp; voltametrijom sa pravougaonim talasima (SWV) i visoko osetljivom adsorptivnom voltametrijom sa pravougaonim talasima (SW-AdSV) u Briton-Robinson puferu, kao pomoćnom elektrolitu, obuhvatajući &scaron;irok opseg pH vrednosti. Odgovor DOX-a primenom&nbsp; Hg(Ag)FE&nbsp;praćen je u intervalu potencijala od -0,20 do -0,80 V.&nbsp; Za analizu tragova, optimizacija metode ukazuje da su optimalni parametri za analitički pik na potencijalu (Ep ) -0,57 V u odnosu na zasićenu kalomelovu elektrodu (ZKE): pH 6,0, potencijal&nbsp; akumulacije -0,20 V i vreme&nbsp; akumulacije 140 s. U model rastvoru, DOX je određivan u koncentracionom opsegu 4,99-59,64&nbsp; ng mL^-1. Razvijena SW-AdSV metoda je primenjena za određivanje DOX-a u obogaćenom uzorku humanog urina. Niža koncentracija DOX-a 9,89ng mL^-1&nbsp;u voltametrijskoj&nbsp; ćeliji je određivana sa relativnom standardnom devijacijom (RSD) manjom od 6,0%. &Scaron;to se ispitivanih makrolida tiče oni su pokazali redukcione signale u dalekoj negativnoj oblasti potencijala. Ispitivanja direktnom katodnom SWV rađena su u opsegu potencijala od -0,75 V do -2,00 V u odnosu na ZKE, pri čemu su dobijena jedan ili dva redukciona pika u opsegu potencijala od -1,5 V do -1,9 V. Oblik i intenzitet signala zavisi od primenjene pH vrednosti u &scaron;irokoj pH oblasti. Za analitičke svrhe, radi razvoja direktne katodne SWV i adsorptivne inverzne/striping SWV metode, pogodnim su se pokazale neutralna i slabo alkalna sredina tj. pH 7,0 sa&nbsp; E_p na -1,67 V u odnosu na ZKE za ROX i EES i pH 7,2 sa E_p na -1,85 V u odnosu na ZKE za AZI i pH 7,4 sa E_p na -1,64 V u odnosu na ZKE za CLA. Na osnovu snimljenih cikličnih voltamograma na&nbsp; optimalnim pH vrednostima, može se predložiti adsorptivno-kontrolisan kinetički proces na elektrodi u slučaju sva&nbsp; četiri ispitivana jedinjenja. Takođe,&nbsp; ¹H NMR merenja uz potiskivanje&nbsp; signala vode u pH oblasti između pH 6,0 i 10,5 ukazuju na to da su makrolidni molekuli pri optimalnim analitičkim uslovima predominantno u protonovanoj formi preko tercijerne amino grupe &scaron;to potpomaže, u sva&nbsp; četiri slučaja, njihovu adsorpciju na odgovarajuće polarizovanoj Hg(Ag)FE. Optimizovane direktne katodne SWV metode&nbsp; pokazuju dobru linearnost u koncentracionom opsegu 4,81-23,3&nbsp; &micro;g mL^-1 , 4,53-29,8&nbsp; &micro;g mL^-1 , 1,96-28,6&nbsp; &micro;g mL^-1 i 1,48-25,9 &micro;g mL^-1 za AZI, EES, CLA odnosno ROX. Razvijene SW-AdSV metode rezultiraju u linearnom odgovoru pri nižim koncentracionim intervalima 1,0-2,46 &micro;g mL^-1 ,&nbsp; 0,69-2,44&nbsp; &micro;g mL^-1, 0,05-0,99 &micro;g mL^-1 i 0,10-0,99&nbsp; &micro;g mL^-1 , za AZI, EES, CLA i ROX. RSD za sve razvijene metode nije veća od 1,5% izuzev SWV metode u slučaju AZI-a gde je 4,5%. Direktna katodna SWV metoda&nbsp; je uspe&scaron;no primenjena za određivanje EES-a u farmaceutskom proizvodu Eritromicin^&reg; dok SW-AdSV metoda je primenjena u slučaju određivanja EES-a u obogaćenom uzorku humanog urina i&nbsp;za određivanje ROX-a u farmaceutskom proizvodu Runac^&reg; . U svim pomenutim slučajevima, primenjena je metoda standardnog dodatka. Pouzdanost i tačnost elaboriranih procedura u slučaju određivanja EES-a u model sistemu i&nbsp; farmaceutskom proizvodu Eritromicin^&reg; su potvrđena poređenjem sa rezultatima dobijenim primenom HPLC-DAD metode.</p><p>Nakon preliminarnih studija 3-dehidro-deoksiholne&nbsp; kiseline/3-dehidro-deoksiholata primenom elektrode od staklastog ugljenika (GCE), gde je uočeno da ne dolazi do formiranja redukcionog signala u Briton-Robinson puferu između pH 5,0 i 11,8 primenom direktne katodne SWV, bizmut-film je izdvojen&nbsp; <em>ex situ</em> na povr&scaron;ini iste elektrode od staklastog ugljenika (BiF-GCE) iz uobičajeno kori&scaron;ćenog rastvora za elektrodepoziciju (0,02 mol L^-1 Bi(NO₃)₃, 1,0 mol L^-1 HCl i 0,5 mol L^-1 KBr) i tako pripremljena elektroda je primenjena za karakterizaciju i određivanje pomenutog jedinjenja u alkalnoj sredini. Redukcioni signal ispitivanog analita od analitičkog značaja je uočen jedino primenom BiF-GCE u Briton-Robinson puferusa pH vrednostima između 9,5 i 11,8 u režimu adsorptivne inverzne/stripingvoltametrije sa pravougaonim talasima, dok u slučaju direktnih katodnih SWV eksperimentalnih uslova uočen je slab redukcioni pik sa niskom strujom maksimuma pika. Optimizovani eksperimentalni uslovi za određivanje 3-dehidro-deoksiholata obuhvataju odgovarajuće kondicioniranje elektrode uključujući kondicioniranje&nbsp; <em>ex situ</em> pripremljene BiF-GCE u Briton-Robinson pomoćnom elektrolitu pH 11,8 do stabilizacije struje bazne linije elektrohemijskim cikliranjem potencijala radne elektrode u potencijalskom opsegu između -1,00 i -2,00 V u odnosu na ZKE (blizu 15 puta) i primenu dva ključna parametara adsorptivne voltametrije sa pravougaonim talasima: vreme akumulacije od 30 s i potencijal akumulacije&nbsp; -1,00 V u odnosu na ZKE. Zbog relativne asimetričnosti dobijenih redukcionih signala ispitivanog analita sa&nbsp; E_p na -1,35 V u odnosu na ZKE, &scaron;to je takođe prisutno i u slučaju primene SW-AdSV, određivanje ispitivanog analita je zasnovano na linearnoj zavisnosti između povr&scaron;ine pika redukcionog signala&nbsp; spitivanog analita i njegove odgovarajuće koncentracije i postignuta granica detekcije je 1,43 &micro;g mL^-1 sa dva linearna opsega kalibracione krive od 4,76 &micro;g mL^-1 do 13,0 &micro;g mL^-1 i od 13,0 &micro;g mL^-1 do 23,1 &micro;g mL^-1 za razvoj analitičke metode. RSD metode je 3,22%. Dodatni eksperimenti, elektroliza ispitivanog analita na potencijalu -1,55 V (blizu maksimuma pika ciljnog analita) u odnosu na ZKE su rađeni primenom GCE u obliku ploče (povr&scaron;ina 33,52 cm 2 ) modifikovane sa&nbsp; <em>ex situ&nbsp;</em>pripremljenim bizmut-filmom. Rastvor od interesa uzorkovan je na početku eksperimenta, nakon 2,5 h i nakon 4,5 h tretmana. Ovakvi uzorci su analizirani primenom ¹H NMR merenja uz potiskivanje signala vode u puferskom rastvoru pH 11,8. Može se pretpostaviti da tokom elektrolize 3-dehidro-deoksiholata dolazi do redukcije keto grupe prisutne u strukturi ispitivanog analita.</p><p>Na osnovu literaturnih podataka da neki od ciljnihmakrolidnih antibiotika kao &scaron;to je npr. azitromicin pokazuju oksidativno pona&scaron;anje na elektrodi od ugljenične paste i elektrodi od zlata deteljna karakterizacija i određivanje&nbsp; četiri makrolidna antibiotika rađena je primenom&nbsp; asične&nbsp;elektrode od ugljenične paste (CPE) koja se sastoji samo od grafitnog praha i parafinskog ulja sa optimizovanih direktnih anodnih SWV metoda. U slučaju EES-a i AZI-a diferencijalna pulsna voltametrija (DPV) je testirana za iste svrhe. Ključni&nbsp; parametar u slučaju razvoja analitičkih voltametrijskih metoda je odabir pH vrednosti pomoćnog elektrolita gde je oblik/simetričnost i intenzitet oskidacionog pika glavni kriterijum prilikom odabira. Kao odgovarajuće pH vrednosti za voltametrijsko određivanje EES-a primenom SWV metode odabrana je pH 8,0 sa E_p na 0,83<br />V u odnosu na ZKE, dok u slučaju DPV metode pH 12,0 sa&nbsp; E_p na 0,55 V u odnosu na ZKE je bila najpogodnija za analitičke svrhe. Za određivanje AZI-a, u slučaju obe SWV i DPV metode pH 7,0 se pokazala najpogodnijom sa E_p analitičkog signala na 0,85 V odnosno 0,80 V u odnosu na ZKE, dok u slučaju CLA i ROX koji su ispitivani samo primenom SWV metode za analitičke svrhe pH 12,0 je bila najpogodnija sredina sa E_p analitičkog signala na 0,65 V odnosno na 0,63 V&nbsp;u odnosu na ZKE. Postignute granice detkcije primenom nemodifikovane CPE i direktne anodne SWV su uglavnom u submikrogramskom koncentracionom opsegu 0,17 &micro;g mL^-1 , 0,32&nbsp; &micro;g mL^-1 i 0,30&nbsp; &micro;g mL^-1, u slučaju EES-a, AZI-a i ROX-a i u niskom mikrogramskom koncentracionom opsegu 1,43&nbsp; &micro;g mL^-1 za CLA. Razvijena SWV metoda sa jednostavnom CPE pokazala se pogodnom za određivanje ROX-a u komercijalnom proizvodu Runac^&reg; tableti. U slučaju optimizovanih DPV metoda postignute granice detekcije za EES i AZI su u niskom mikrogramskom&nbsp; koncentracionom opsegu 1,03&nbsp; &micro;g mL^-1 odnosno 1,53&nbsp; &micro;g&nbsp; mL^-1 . U želji da se&nbsp;postigne niža granica detekcije za AZI, DPV metoda&nbsp; je testirana u kombinaciji sa&nbsp; CPE radnom elektrodom povr&scaron;inski modifikovanom sa zlatnim nanočesticama&nbsp; prečnika 10 nm (Au-CPE) i&nbsp; postignuta granica detekcije je 0,95&nbsp; &micro;g mL^-1 sa&nbsp; E_p analitičkog signala na 0,80 V u odnosu na&nbsp; ZKE. RSD metode u slučaju Au-CPE je 3,5%, dok je u slučaju nemodifikovane CPE 6,0%.&nbsp; Linearnost analitičke metode zasnovane na primeni Au-CPE je dva puta &scaron;ira nego u slučaju&nbsp; primene nemodifikovane CPE.</p><p>Na osnovu dobijenih rezultata može se zaključiti da&nbsp; odgovarajuće kombinacije&nbsp; optimizovanih voltametrijskih tehnika sa ekolo&scaron;ki prihvatljivim i lako primenljivim radnim&nbsp; elektrodama, kao &scaron;to su Hg(Ag)FE, BiF-GCE i CPE zajedno sa Au-CPE, rezultuju razvojem&nbsp; pouzdanih analitičkih metoda, kako u oksidacionim tako i u redukcionim proučavanjima, koje&nbsp; često omogućuju&nbsp; određivanje tragova analita od farmakolo&scaron;kog značaja u jednostavnim, a u&nbsp;nekim slučajevima i u složenim sistemima.&nbsp;</p> / <p>Nowadays in different analytical laboratories there is the increasing number of analytical protocols, either based on highly sophisticated or simpler measurements techniques, which serving for determination of different target analytes of pharmacological importance. Among such target groups of the analyte belongs the antibiotics which present a great discovery in the field of medicine and thanks to them were saved more than seven million people but beside to the mentioned great benefits, antibiotics can cause a large number of side effects and bile acids together with their derivatives which are physiological detergents but if their concentration is not<br />controlled they can be cytotoxic to the body. In the present doctoral dissertation the development of analytical methods, primarily analytical voltammetric methods in combination with simple and contemporary electrodes/sensors, for the determination of selected analytes as antracycline antibiotic doxorubicin (DOX), macrolide antibiotics erythromycin ethylsuccinate (EES), azithromycin (AZI), clarithromycin (CLA) and roxithromycin (ROX) and 3-dehydrodeoxycholic acid were performed.</p><p>Voltammetric characterization and determination of the above mentioned antibiotics using a renewable silver-amalgam film electrode (Hg(Ag)FE) was performed by direct cathodic square-wave voltammetry (SWV) and by highly sensitive adsorptive square-wave voltammetry (SW-AdSV) in aqueous Britton-Robinson buffer solutions as supporting electrolyte covering the wider pH range. The Hg(Ag)FE response of DOX was monitored in the potential range between -0.20 and -0.80 V. For the trace level analysis the method optimization showed that the optimal conditions for the analytical peak with peak potential (E_p) at -0.57 V vs. SCE were: the pH 6.0, the accumulation potential -0.20 V, and the accumulation time 140 s. In the model solutions, DOX was determined in the concentration range of 4.99-59.64 ng mL^-1. The developed SWAdSV method was applied for the determination of DOX in spiked human urine sample. The lowest concentration of DOX of 9.89 ng mL^-1 in voltammetric vessel was determined with the relative standard deviation (RSD) less than 6%. As for the investigated macrolides, they showed reduction signals in fairly negative potential range. During direct cathodic SWV investigations conducted over the potential range from -0.75 V to -2.00 V vs. SCE, either one or two reduction peaks were obtained in the&nbsp; potential range from -1.5 to -1.9 V. For analytical purposes concerning the development of direct cathodic SWV and adsorptive stripping SWV methods the neutral&nbsp; and slightly alkaline media were suitable as pH 7.0 with E_p at -1.67 V vs.&nbsp; SCE for ROX and EES and pH 7.2 and pH 7.4 with E_p at -1.85 V and -1.64 V vs. SCE for AZI and CLA, respectively. Based on the cyclic voltammograms recorded at these pH values, adsorptioncontrolled electrode kinetics process can be proposed for all four investigated compounds. The water suppressed ¹H NMR measurements in the pH range between 6.0 and 10.5 indicated that the macrolide molecules at the optimal analytical conditions are predominantly in protonated form via their tertiary amino groups which supported in all four cases their adsorption on the appropriately polarized Hg(Ag)FE electrode. The optimized direct cathodic SWV methods showed good linearity in concentration ranges 4.81-23.3 &mu;g mL^-1, 4.53-29.8 &mu;g mL^-1, 1.96-28.6&nbsp; &mu;g mL^-1, and 1.48-25.9 &mu;g mL^-1 for AZI, EES, CLA and ROX, respectively. The SW-AdSV methods resulted in the linear responses at lower concentration ranges as 1.0-2.46 &mu;g mL^-1, 0.69- 2.44 &mu;g mL^-1, 0.05-0.99 &mu;g mL^-1 and 0.10-0.99 &mu;g mL^-1, for AZI, EES, CLA and ROX, respectively. The RSD for all developed methods was not higher than 1.5% except the SWV method for AZI with 4.7%. The direct cathodic SWV method was successfully applied for the determination of EES in the pharmaceutical preparation Eritromicin^&reg;, while SW-AdSV was tested in the case of the spiked urine sample and for determination of ROX in pharmaceutical preparation Runac^&reg;. In all above cases, the standard addition method was used. The reliability and accuracy of the above procedures in the case of EES determination in model system and pharmaceutical preparation Eritromicin^&reg; were validated by comparing them with those obtained by means of HPLC-DAD measurements.</p><p>After initial study of 3-dehydro-deoxycholic acid/3-dehydro-deoxycholate by glassy carbon electrode, where the absence of any reduction peak was observed in the Britton-Robinson buffer solutions between pH 5.0 and 11.8 by direct cathodic SWV, a bismuth-film was electrodeposited ex situ on the same glassy carbon electrode surface (BiF-GCE) from the usually used plating solution (0.02 mol L^-1 Bi(NO₃)₃, 1.0 mol L^-1 HCl and 0.5 mol L^-1 KBr) and such prepared film-electrode was applied for the characterization and determination of the the target analyte in alkaline media. The reduction signal of analytical importance was observed only by BiF-GCE in Britton-Robinson buffer solutions with pH values between 9.5 and 11.8 in adsorptive stripping square-wave voltammetry working regime, while in the case of the direct cathodic SWV experimental protocol only a very poor reduction peak was obtained. The optimized experimental conditions for the 3-dehydro-deoxycholate determination consist of the optimized electrode conditioning including the electrochemical cycling of the <em>ex situ </em>prepared BiF-GCE potentials in the potential span between -1.0 and -2.0 V vs. SCE (nearly 15 times) in the Britton-Robinson supporting electrolyte pH 11.8 till the stabilization of the baseline current, and the application of two key parameters of the adsorptive square-wave voltammetric protocol: the accumulation time as 30 s and accumulation potential as -1.0 V vs. SCE. Because of the relative asymmetry of the obtained reduction signals of the target analyte with peak E_p at -1.35 V vs. SCE, which is still present in the case of the SW-AdSV, the quantification of the target analyte was based on the linear correlation between peak area of the reduction signal and its appropriate concentrations, and reached limit of detection is 1.43 &mu;g mL^-1 and with two linear ranges of calibration curve from 4,76 &mu;g mL^-1 to 13.0 &mu;g mL^-1 and from 13,0 &mu;g mL^-1 to 23,1 &mu;g mL^-1 for the development of analytical method. The RSD of the method&nbsp; was 3.22%. Additional experiments were performed applying GCE with rectangular form (area 35.32 cm²) modified with ex situ prepared bismuth-film for the electrolysis of the target analyte which was performed at the potential -1.55 V (nearly the peak maxima of the target analyte) vs. SCE. The solution of interest was sampled at the beginning of the experiment, after 2.5 h and after 4.5 h of treatment. Such samples were analysed by simply water suppressing ¹H NMR measurements in the buffered solution at pH 11.8. It can be assumed that during electrolysis of 3-dehydrodeoxycholate the reduction of the keto group present in the structure of the target analyte can be occurred.</p><p>Driven by earlier literature data about the fact that some of the target macrolide antibiotics as e.g. azithromycin showed oxidation behavior at a carbon paste and gold working electrodes detailed characterization and determination of four target macrolide antibiotics were performed on classical carbon paste electrode (CPE) constituted only from graphite powder and paraffin oil with optimized direct anodic SWV methods. In the cases of EES and AZI differential pulse voltammetric (DPV) methods were tested for the same purpose as well. The key parameter in the case of the development of the analytical voltammetric methods is the selection of the pH value of the supporting electrolyte where the shape/simmetry and intensity of the oxidation peak were the criteria. As the appropriate pH value for determination of EES by SWV method the pH 8.0 was selected with E_p at 0.83 V vs. SCE while in the case of the DPV method the pH 12.0 with E_p at 0.55 V vs. SCE was the most suitable for analytical&nbsp; purpose. As for AZI determination, in the case of both SWV and DPV methods the pH 7.0 was the most appropriate supporting electrolyte with the Ep of analytical signal at 0.85 V and 0.80 V vs. SCE, respectively, while in the case of CLA and ROX which were investigated only with SWV method for the analytical purposes the pH 12.0 was the most suitable with E_p at 0.65 V and at 0.63 V vs. SCE. The obtained detection limits applying the bare CPE and the direct anodic SWV are mainly&nbsp; in submicrogram concentration range as 0.17 &mu;g mL^-1; 0.32 &mu;g mL^-1 and 0.30 &mu;g mL^-1 for EES, AZI, and ROX and in the low microgram concentration range as 1.43 &mu;g mL^-1 for the CLA, respectively. The developed method succesfully tested for the determination of ROX in the commercial formulation, Runac^&reg; tablet. In the case of the optimized DPV methods the obtained detection limits for EES and AZI are in the low microgram concentration range 1.03 &mu;g mL^-1 and 1.53 &mu;g mL^-1, respectively. For the improvement of the sensitivity for AZI the DPV method was tested in combination with a&nbsp; CPE working electrode surface modified with gold nanoparticles with diameter of 10 nm (Au-CPE) and reached the limit of detection was 0.95 &mu;g mL^-1 at E_p of 0.80 V vs. SCE. The RSD of the method in the case of the Au-CPE is 3.5% while in the case of the native CPE 6.0%. The linearity of the Au-CPE based analytical method is twice wider then it is case with the bare CPE applying protocol.</p><p>Based on the obtained results it can be conclude that the appropriate combination of the optimized voltammetric pulse techniques and the environmentally friendly and easy to use working electrodes as Hg(Ag)FE, BiF-GCE and CPE together with Au-CPE resulted in the development of reliable analytical method either in the oxidation or reduction studies, often allowing trace level determination of pharmacological importance target analytes in simpler and in some case complexes systems.</p>

This diploma thesis is focused on the determination of chloramphenicol by differential pulse voltammetry (DPV), DC voltammetry (DCV), cyclic voltammetry (CV) and adsorptive stripping voltammetry (AdSV) on a meniscus modified silver solid amalgame electrode (m- AgSAE). For the determination of chloramphenicol the optimum conditions were found and under these conditions concentration dependences were measured and then limits of quantification were determined. The influence of pH of BR buffer was tested. For determination of chloramphenicol by DCV pH 7 was chosen as an optimum background and pH 8 was chosen as an optimmum for DPV determination. Under these conditions linear dependences were obtained in the concentration range of 1·10-6 - 1·10-4 mol·l-1 . The limit of detection of chloramphenicol by DCV was 2.3·10-6 mol·l-1 . The limit of detection of chloramphenicol by DPV was 2.1·10-6 mol·l-1 in distilled water, 2.9·10-6 mol·l-1 in river water and 4.2·10-6 mol·l-1 in drinking water. Electrochemical behavior of chloramphenicol was studied by cyclic voltammetry in BR buffer with pH 2, 6, 8, 12 and then mechanism of reduction of chloramphenicol was propose based on available literature. Chloramphenicol was determined in drug Spersadex by DPV in BR buffer with pH 8. The optimal conditions for determining...

2-Nitrofluorene is a model representative of nitrated polycyclic aromatic hydrocarbons (NPAH) which belongs to a group of mutagens and carcinogens. Interaction of DNA with genotoxic 2-nitrofluorene was monitored by an electrochemical DNA biosensor made of a glassy carbon electrode (GCE) and low molecular weight DNA from salmon sperm. Techniques used are electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV) and square-wave voltammetry (SWV). Using the EIS technique, no damage to DNA, which would cause strand breaks in DNA, was observed, whereas using the CV technique, the intercalation of NF to the structure of DNA was observed, leading to the formation of a NF-DNA complex. The intercalation results in a reduction of electroactive sites which can be oxidized. It was verified using the SWV technique, by which a decrease of the peak heights of adenosine and guanosine was observed. Because of the dangerous effect of NF on the structure of DNA, an electroanalytical method for its determination was developed. An applicability of the method was successfully tested on a model sample of sand. For the development of the technique, differential pulse voltammetry (DPV) was used in a mixture of the Britton-Robinson buffer of pH 7.0 and ethanol in a ratio of 7:3 (v/v) and with a periodic...

of the Diploma Thesis In this Diploma Thesis, the electrochemical behavior of 4-nitrophenol (4-NP) was studied at a newly prepared large-surface carbon film electrode (ls-CFE) using techniques of DC voltammetry (DCV) and differential pulse voltammetry (DPV) with the aim to develop sensitive analytical methods for its determination. Voltammetric behavior of 4-NP was investigated in the region of anodic potentials, in dependence on the pH of the medium used (realized using Britton-Robinson buffer). The optimum pH values for the determination of 4-NP were chosen as follows: pH 3.0 (for DCV) and pH 7.0 (for DPV). During anodic oxidation of 4-NP on the ls-CFE at the concentration of the analyte of 1·10-4 mol/l, the passivation of the electrode surface occurred. Thus, it was decided to record series of measurements always at a new carbon film. Using the sample of 4-NP (at the concentration of 1·10-4 mol/l), the repeatability of the application of individual carbon films was tested, with obtained RSD values of 3.7% and 3.6% for DCV and DPV, respectively. Under optimum conditions, the calibration dependences of 4-NP were measured in the concentration range from 1·10-6 to 1·10-4 mol/l, with the limits of quantification (LQs) of 1.5·10-6 mol/l (for DCV at the ls-CFE) and 4.6·10-7 mol/l (for DPV at the...

This master's thesis is focused on the determination of 6-thioguanine (6-T) by DC voltammetry (DCV), differential pulse voltammetry (DPV) and flow injection analysis with electrochemical detection (FIA-ED) on a boron doped diamond electrode (BDDFE). The optimum conditions for determination of 6-T were found and under these conditions, concentration dependences were measured and the limits of quantification (LOQ) were calculated for each method. Medium of 60% methanol and phosphate buffer (PB) pH 2,0 was chosen as optimum for DCV and DPV determination of 6-T at BDDFE. For both DCV and DPV, the linear concentration dependences were obtained in concentration ranges of 6-T from 2 µmol·l-1 to 10 µmol·l-1 with LOQ 0,9 µmol·l-1 for DCV and 1,5 µmol·l-1 for DPV. Lower LOQ was achieved in PB pH 2,0, where LOQ was 0,6 µmol·l-1 for both DCV and DPV, but the problem was lower repeatability. In PB pH 2 6-T was determined by DCV in drinking and river water with LOQ 1,3 µmol·l-1 in both drinking and river water. The possibility of solid phase extraction was investigated as a method for preliminary separation of 6-T from urine. For FIA under optimized conditions (polarization potential 1300 mV, flow rate 5 ml·min1 and sample volume 50 µl) the linear concentrations dependences were obtained in concentration ranges...

The submitted work deals with the application of voltammetric determination of Fomesafen using non-traditional mercury meniscus modified silver solid amalgam electrode on model samples of Fomesafen in real aqueous matrices of drinking and river water. This method of measurement has been developed and optimized in my bachelor thesis, which the diploma thesis is related to. Fomesafen belongs to a group of herbicides used on a mass scale in the late 20th century in the USA and in many countries around the world still used even today. Among its side effects according to the EPA include, among others, potential carcinogenicity to humans and confirmed carcinogenicity to some mammals (such as rats) which led to a legislative regulation on its use in many countries around the world including the USA, the European Union and many others. Silver solid amalgam electrode has been developed with the intention to limit the use of mercury in accordance with new legislation of the European Union and the concept of green analytical chemistry. Despite the low levels of mercury mainly bound in the form of virtually harmless silver amalgam electrode retains very similar electrochemical properties with proven mercury electrodes. As part of the thesis, direct determination of a number of partial extraction of Fomesafen...

<p>Predmet istraživanja ove disertacije predstavlja unapređenje, modelovanje i optimizacija procesa elektroerozivne obrade (EDM) savremenih inženjerskih materijala. Prvo su predstavljene dve inovativne metode: EDM u dielektrikumu sa pome&scaron;anim prahom i EDM sa pomoćnom elektrodom, a zatim i njihova kombinacija. Za generisanje matematičkih modela primenjene su metodologija odzivne povr&scaron;ine i alati ve&scaron;tačke inteligencije. U nastavku su postavljeni optimizacioni procesi određivanja ulaznih parametara sa jednom i vi&scaron;e funkcija cilja koji su re&scaron;eni primenom klasičnih metoda optimizacije. U zavr&scaron;nom osvrtu sprovedena je verifikacija dobijenih modela i optimalnih ulaznih parametara elektroerozivne obrade.</p> / <p>The subject of the research of this dissertation is the improvement, modeling and optimization of the electrical discharge machining (EDM) of advanced engineering materials. First, two innovation methods are presented: EDM in powder mixed dielectric fluid and EDM with assisted electrode and that their combination. The method of response surface and artificial intelligence tools were applied to generate mathematical models. The optimization problems of determining the input parameters with single and multiple target functions are solved by the application of classical optimization methods. Finally, verification of the obtained models and optimal input parameters of electrical discharge machining was carried out.</p>

This diploma thesis deals with problematics of electrochemical power sources with focus on lithium accumulators, their construction and functioning priciple. It also discusses the safety of li-ion batteries with respect to their flammability. In addition, the flame retarders, which help to lower the flammability, are listed. The thesis describes Cyclic Voltammetry and Galvanostatic Cycling with Potencial which are lithium-ion cell measuring methods. In the last part, the influence of various flame retarders on negative electrode is compared based on the conducted tests.

This work focuses on sodium-ion batteries. It describes the basic principles of accumulators, focusing more on secondary cells, their electrodes, especially negative electrodes. The work is lightly based on the basics of lithium-ion batteries. The practical part of the work is the production of negative electrodes Na2Ti3O7, which are further measured at three different temperatures. These measurements are then evaluated.