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In this work, carbon paste electrode (CPE) and carbon paste electrode modified with gold nanoparticles (AuNPs/CPE) were employed with rapid direct anodic square wave voltammetry (SWV) for macrolide antibiotics erythromycin ethylsuccinate (EES), azithromycin (AZI), clarithromycin (CLA) and roxithromycin (ROX) determination. The surfaceof working electrodes was morphologically characterized by scanning electron microscopic (SEM) measurements whereby the presence of randomly distributed AuNPs of 10 nmdiameter size on CPE surface was confirmed by energy dispersive spectrometer (EDS). SWV determination of four macrolide antibiotics using CPE was performed in aqueous Britton-Robinson buffer solutions (pH 2.0 to 11.98) showing that oxidation signals strongly depend upon pH (at pH ≥ 6) and exhibited the most favorable characteristics at pH 8.0 in the case of EES and pH 11.98 in the case of AZI, CLA and ROX. Under optimized conditions, the SWV method using CPE enables determination of all investigated macrolide antibiotics in low μg mL−1 concentration ranges with relative standard deviations (RSDs) lower than 6%and achieved detection limits (LODs) as 0.18, 0.045, 1.43 and 0.30 μgmL−1 for EES, AZI, CLA and ROX, respectively. In the case of AZI and ROX, it was demonstrated that the use of AuNPs/CPE as working electrode could additionally improve the results obtained with the SWV method concerning exhibited sensitivity, reproducibility and linear concentrationrange, due to the electrocatalytic properties of synthesized AuNPs. The optimized experimental parameters with the use of SWV method and CPE or AuNPs/CPE were successfully applied for determination of ROX and AZI in their pharmaceutical preparations Runac® and Hemomycin®, respectively. The reliability of the elaborated procedures and thus the accuracy of the obtained results were validated by comparing them with those obtained by means of HPLC-DAD measurements.

Danas, u raznim analitičkim laboratorijama postoji veći broj analitičkih protokola, zasnovanih bilo na izuzetno sofisticiranim ili jednostavnijim tehnikama, koji služe za određivanje različitih ciljnih analita od farmakološkog značaja. Među tim grupama ciljnih analita pripadaju i antibiotici koji predstavljaju veliko otkriće u oblasti medicine i zahvaljujući njima spašeno je više od sedam miliona života, ali pored navedenih koristi, antibiotici mogu da izazovu veliki broj neželjenih efekata i žučne kiseline zajedno sa svojim derivatima, koji su fiziološki deterdženti, mogu biti citotoksične za organizam ako se njihova koncentracija ne kontroliše. U ovoj doktorskoj disertaciji prikazan je razvoj analitičkih metoda pre svega voltametrijskihmetoda u kombinaciji sa jednostavnim i savremenim elektrodama/senzorima za određivanje odabranih analita kao što je antraciklični antibiotik doksorubicin (DOX), makrolidni antibiotici eritromicin-etilsukcinata (EES), azitromicina (AZI), klaritromicina (CLA) i roksitromicina (ROX) i 3-dehidro-deoksiholne kiseline. Voltametrijska karakterizacija i određivanje gore navedenih antibiotika primenom obnovljive srebro-amalgam film elektrode (Hg(Ag)FE)rađena je direktnom katodnom voltametrijom sa pravougaonim talasima (SWV) i visoko osetljivom adsorptivnom voltametrijom sa pravougaonim talasima (SW-AdSV) u Briton-Robinson puferu, kao pomoćnom elektrolitu, obuhvatajući širok opseg pH vrednosti. Odgovor DOX-a primenom Hg(Ag)FE praćen je u intervalu potencijala od -0,20 do -0,80 V. 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 akumulacije -0,20 V i vreme akumulacije 140 s. U model rastvoru, DOX je određivan u koncentracionom opsegu 4,99-59,64 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 u voltametrijs, 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 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. 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 (Ep) 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 de

The renewable silver-amalgam film electrode (Hg(Ag)FE) was applied for voltammetric characterization and determination of semi-synthetic macrolide antibiotics azithromycin (AZI), clarithromycin (CLA) and roxithromycin (ROX) in the Britton-Robinson buffer as supporting electrolyte ranging the pH from 4.0 to 11.9. All three macrolides showed reduction signals in fairly negative potential range. During direct cathodic square wave voltammetric (SWV) investigations conducted over the potential range from -0.75 V to -2.00V vs SCE, either one or two reduction peaks were obtained in the potential range from -1.5 to -1.9 V. The shapes and intensities of the signals depend on the applied pH values in wider pH ranges. For analytical purposes concerning the development of direct cathodic SWV and adsorptive stripping SWV (SW-AdSV) methods the neutral and slightly alkaline media were suitable as pH 7.2, pH 7.4 and pH 7.0 for AZI, CIA and ROX, respectively. Based on the cyclic voltammograms recorded at these pH values, adsorption-controlled electrode kinetics process can be proposed for all three macrolides. Furthermore, the water suppressed H-1 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 three 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 gmL(-1), 1.96-28.6 mu gmL(-1) and 1.48-25.9 mu gmL(-1) for AZI, CIA and ROX, respectively. The development of the SW-AdSV methods resulted in the linear responses at lower concentration ranges as 1.0-2.46 mu gmL(-1), 0.05-0.99 mu gmL(-1) and 0.10-0.99 mu gmL(-1), for AZI, CIA and ROX, respectively. The relative standard deviation for all developed methods was not higher than 1.0% except the SWV method for AZI with 4.7%. In the case of all three

Erythromycin, a macrolide antibiotic, has similar antimicrobial spectrum to penicillin and it is widely used, especially in the treatment of patients who are allergic to penicillin. In this work, the application of a renewable silver-amalgam film electrode (Hg(Ag)FE) for the characterization and determination of erythromycin ethylsuccinate (EES), a widely used esterified form of this antibiotic, by means of cyclic voltammetry (CV) and square wave voltammetry (SWV) is presented. In the aqueous Britton-Robinson buffer (pH 5.0-9.0) that served as the supporting electrolyte, one reduction peak of EES was observed in the investigated potential range between -0.75 V and -1.80 V vs SCE, with peak potential maxima ranging from -1.59 V to -1.70 V, which strongly depended on the applied pH, as did the peak shape. For the analytical purposes the pH of 7.0 was selected, since in this electrolyte the EES peak was well-shaped and separated from the background current of the supporting electrolyte in both cases; in the direct cathodic SWV and in the case of square wave adsorptive stripping voltammetry (SW-AdSV). It was established, by the E-p-pH correlation, that protons strongly influenced the electrochemical reduction of EES. The CVs recorded between 0.025-0.50 V s (1) at pH 7.0 confirmed that the electrode reaction is adsorption-controlled. Based on the series of H-1 NMR measurements it is proved that the tertiary amino group of EES is mainly in its protonated form at pH 7.0 which may lead, at appropriate accumulation potential and time, to the favored adsorption of the target ionic form of the analyte improving on such way the sensitivity of the SW-AdSV method. The optimized procedures resulted in stable SWV responses with good linear correlation in the EES concentration range from 4.53 to 29.8 mu g mL (1) (LOD = 1.36 mu g mL (1)), and from 0.69 mu g mL (1) to 2.44 mu g mL (1) (LOD 0.21 mu g mL (1)) in the case of optimized SW-AdSV. The relative standard deviation is below 1.5