Abstract
High performance liquid chromatography coupled with triple-quadrupole mass spectrometry was applied in the determination of in vitro metabolism products of selected antibiotic drugs (cefotaxime, ciprofloxacin, fluconazole, gentamicin, clindamycin, linezolid, and metronidazole). The analytes were separated on a reversed phase C18 column, with acetonitrile and 0.1 % aqueous formic acid as the mobile phase. Tandem mass spectrometry with positive electrospray ionization was used to facilitate the structural characterization of the potential metabolites. Metabolism studies on human liver microsomes were performed via cytochromes P450 (phase I) and via NADPH/UDP-glucuronosyltransferase (phase II) mediated reactions. LC-MS/MS experiments allowed potential metabolite peaks, including sum formulae suggestions, to be identified; high resolution MS/MS experiments led to the identification of various oxidative and reductive modifications of target compounds in phase I biotransformation, and conjugation products with glucuronic acid in phase II reactions. A total of 11 potential metabolites and their proposed structures were characterized during the incubation of human liver microsomes by comparing their retention times and spectral patterns with those of the parent drug. Dehydrogenation and reactions of side chains such as hydroxylation and hydrolysis of ester bonds constituted the major metabolic pathways. Finally, LC-MS/MS spectrometry was revealed to be a suitable analytical tool to procure a feasible analytical base for the envisioned in vivo experiments. Graphical Workflow overview of in vitro drug metabolism studies. Electronic supplementary materialThe online version of this article (doi:10.1007/s00216-016-9929-6) contains supplementary material, which is available to authorized users.
Highlights
IntroductionA significant interest regarding bacterial infections could be observed
In recent years, a significant interest regarding bacterial infections could be observed
In vitro incubation of selected antibiotic drugs with human liver microsomes Human liver microsomes were applied during performed investigation
Summary
A significant interest regarding bacterial infections could be observed. TDM will be more valuable, which will make it possible to personalize and optimize therapeutic practices and healthcare system. In view of the diverse and unique pharmacokinetic profile of drugs in patients undergoing treatment for bacterial infections, there is a need to use TDM in an attempt to optimize the exposure to antibiotics, improve clinical outcome, and limit the alarming occurrences of antibiotic resistance in bacteria [1,2,3]. Antibiotics are a class of antimicrobials, a larger group that includes anti-viral, anti-fungal, and anti-parasitic drugs. They are among the most frequently prescribed medications in modern medicine. There is a wide range of antibiotics, and the choice of what to administer to a patient depends on which kind of infection it is and which types of antibiotics are known to be effective against it as different classes of antibiotics combat bacterial infections in different ways
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