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Abstract Introduction
Nowadays, some clinical outcomes of patients treated with antibiotic drugs strongly suggest their therapeutic drug monitoring (TDM) in order to assess efficacy, compliance and side-effects.Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) is now recognized as pivotal for measuring any xenobiotic molecule in biological fluid. However, besides the incontrovertible advantages of accuracy, precision and cost-effectiveness of LC-MS/MS, there is usually the need to rely on an isotopically-labeled internal standard for mitigating any matrix and/or recovery issues. Nonetheless these labeled compounds can pose availability and cost constraints when related to newly-introduced pharmaceutical drugs.
Objectives
The hereby-presented protocol is centered on a new application kit and relies on a special plumbing which implements a fast on-line sample cleaning.
Method
The LC-MS/MS approach, characterized by a fair chromatographic capacity factor value (K), enables the simultaneous measurement of Vancomycin, Gentamicin, Amikacin, Linezolid and Teicoplanin, on protein-precipitated plasma and with a non isotopically-labelled compound proposed as for internal standard.
Results
Ion-suppression effect has been assessed meanwhile overall matrix effect has been less than 6.5%. With a linearity tested in the respective ranges for the five drugs (R² = 0.999 for Gentamicin C1 between 0.045-2.25 ug/mL, the lowest range), method comparison with immunometric measurements on 30 patient samples has given an equation: y = 0,8837x + 1,5154 (R² = 0,9956) for Amikacin on plasma samples spanning between 1.0 and 100 ug/mL; and an equation: y = 0,8861x + 3,2712 (R² = 0,9544) for Vancomycin on samples spanning between 20 and 40 ug/mL.
Conclusion
The LC-MS/MS setting has allowed to split and measure the main components of Gentamicin, an aminoglycoside, and of Teicoplanin, a glycopeptide, for supporting any study related to alleged different antimicrobial potency of single components. |