Retention and ionization behavior of selected glycopeptide antibiotics for their analytical and bioanalytical study using an UHPLC-MS/MS method with a chemometrical approach

[A. D. Stajić]

94, 10 str.

Analitika lekova - Analitika lekova / Drug Analysis - Drug Analysis

Vankomicin i teikoplanin pripadaju grupi glikopeptidnih antibiotika koji se danas široko primenjuju u terapiji teških infekcija izazvanih multirezistentnim gram-pozitivnim bakterijama. Teikoplanin predstavlja smešu šest komponenata i to: teikoplanin A3-1, teikoplanin A2-1, teikoplanin A2-2, teikoplanin A2-3, teikoplanin A2-4 i teikoplanin A2-5 Cilj ove doktorske disertacije jeste sveobuhvatna studija retencionog i jonizacionog ponašanja vankomicina i svih šest oblika teikoplanina u sistemu UPLC sa tandemskom masenom spektrometrijom kako bi proces njihove analitike i bioanalitike bio unapređen. Prvi deo istraživanja podrazumevao je opisivanje retencionog ponašanja pomenutih antibiotika u UPLC sistemu i jonizacionog ponašanja u masenom spektrometru. Zatim je postavljena UPLC-MS/MS metoda u skladu sa AQbD konceptom, a u cilju praćenja šest oblika teikoplanina (teikoplanin A3-1, teikoplanin A2-1, teikoplanin A2-2, teikoplanin A2-3, teikoplanin A2-4 i teikoplanin A2-5), njegove farmakopejske nečistoće, kao i vankomicina u odgovarajućim farmaceutskim oblicima. Data metoda primenjena je u analizi odgovarajućih farmaceutskih oblika, kao i za sistematičnu procenu i praćenje stabilnosti teikoplanina i vankomicina. Drugi deo doktorske disertacije posvećen je postavljanju nove UHPLC-MS/MS metode za analizu vankomicina i šest oblika teikoplanina u uzorcima humane plazme. AQbD koncept je implementiran kroz nekoliko tačno definisanih faza, u okviru kojih je, u cilju preciznog odabira hromatografskog optimuma, primenjen hemometrijski pristup. Implementacija AQbD pristupa omogućila je razvoj brze metode željenih karakteristika i kvaliteta čime je analitika pomenutih antibiotika znatno pouzdanija i preciznija, a istovremeno znanje iz oblasti masene spektrometrije dosta unapređeno.

Vancomycin and teicoplanin belong to the glycopeptide antibiotics group that are widely used today in the treatment of severe infections caused by multiresistant gram-positive bacteria. Teicoplanin is a mixture of six components: teicoplanin A3-1, teicoplanin A2-1, teicoplanin A2-2, teicoplanin A2-3, teicoplanin A2-4 and teicoplanin A2-5 The goal of this doctoral dissertation is a comprehensive study of the retention and ionization behavior of vancomycin and all six forms of teicoplanin in the UHPLC system with tandem mass spectrometry with the aim to improve the process of their analysis and bioanalysis. The first part of the research involved describing the retention behavior of the mentioned antibiotics in the UHPLC system and the ionization behavior in the mass spectrometer. After that UHPLC-MS/MS method was set up in accordance with the AQbD concept, and in order to monitor six forms of teicoplanin (teicoplanin A3-1, teicoplanin A2-1, teicoplanin A2-2, teicoplanin A2-3, teicoplanin A2-4 and teicoplanin A2- 5), its pharmacopoeial impurity, as well as vancomycin in appropriate pharmaceutical forms. The given method was applied in the analysis of appropriate pharmaceutical forms, as well as for the systematic assessment and stability monitoring of teicoplanin and vancomycin. The second part of the doctoral dissertation is dedicated to setting up a new UHPLC-MS/MS method for the analysis of vancomycin and six forms of teicoplanin in human plasma samples. The AQbD concept was implemented through several precisely defined phases, within which, in order to precisely select the chromatographic optimum, a chemometric approach was applied. The implementation of the AQbD approach enabled the development of a fast method of the desired characteristics and quality, which makes the analysis of the mentioned antibiotics significantly reliable and precise, and at the same time the knowledge in the field of mass spectrometry has been greatly improved.

teikoplanin, vankomicin, hemometrija, masena spektrometrija, AQbD, razvoj metode, priprema uzorka

teicoplanin, vancomycin, chemometrics, mass spectrometry, AQbD, method development, sample preparation

615.28:543.51(043.3)

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