= Discovery stage.
= Translation stage.
= Clinically available.
MSACL 2019 EU : Martini

MSACL 2019 EU Abstract

Self-Classified Topic Area(s): Small Molecules / Tox / TDM

An LC-MS/MS Method for Simultaneous Measurement of Five Antimicrobial Drugs (Vancomycin, Gentamicin, Amikacin, Linezolid and Teicoplanin) for TDM

Martini A. (1), Mirri P. (1), Casetta F. (2), Albertini M. (2), Sandroni F. (2), Clerici P. (1)
(1) ASST Ovest Milanese– Legnano, Italy; (2) B.S.N. – Castelleone, Italy


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 Antonio Martini (Presenter)
ASST OVEST MILANESE;CLINICAL LAB. Legnano Hospital

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Presenter Bio: Graduated in Chemistry; Chief of Chromatography Lab; Clinical Pathology Department

Relevant Financial Disclosures (within past 24 months)
No relevant financial relationship(s) to disclose.

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.