Validation and Clinical Application of a New Liquid Chromatography Coupled to Mass Spectrometry (HPLC-MS) Method for Dalbavancin Quantification in Human Plasma
Valeria Avataneo,
Miriam Antonucci,
Elisa Delia De Vivo,
Antonio Briozzo,
Jessica Cusato,
Francesca Bermond,
Corrado Vitale,
Francesco Vitale,
Alessandra Manca,
Alice Palermiti,
Giovanni Di Perri,
Francesco Giuseppe De Rosa,
Amedeo De Nicolò,
Antonio D’Avolio
Affiliations
Valeria Avataneo
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, 10149 Turin, Italy
Miriam Antonucci
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, 10149 Turin, Italy
Elisa Delia De Vivo
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, 10149 Turin, Italy
Antonio Briozzo
Department of Internal Medicine, A.O. Umberto I Ordine Mauriziano, 10128 Turin, Italy
Jessica Cusato
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, 10149 Turin, Italy
Francesca Bermond
Nephrology and Dialysis, A.O. Ordine Mauriziano di Torino, 10128 Turin, Italy
Corrado Vitale
Nephrology and Dialysis, A.O. Ordine Mauriziano di Torino, 10128 Turin, Italy
Francesco Vitale
Department of Internal Medicine, A.O. Umberto I Ordine Mauriziano, 10128 Turin, Italy
Alessandra Manca
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, 10149 Turin, Italy
Alice Palermiti
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, 10149 Turin, Italy
Giovanni Di Perri
Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, 10149 Turin, Italy
Francesco Giuseppe De Rosa
Unit of Infectious Diseases, Department of Medical Sciences, University of Turin, 10149 Turin, Italy
Amedeo De Nicolò
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, 10149 Turin, Italy
Antonio D’Avolio
Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, 10149 Turin, Italy
Dalbavancin (DBV) is an intravenous long-acting second-generation glycolipopeptide antibiotic with high efficacy and excellent tolerability, approved for use in the treatment of Gram-positive skin and skin structure infections (ABSSSI). Nevertheless, little is known about its pharmacokinetic/pharmacodynamic (PK/PD) properties in real life, which is also due to technical challenges in its quantification in human plasma, preventing an effective application of therapeutic drug monitoring (TDM). In fact, DBV has a high affinity to plasma proteins, possibly resulting in poor recovery after extraction procedure. The aim of this study was to validate a simple, cheap and reliable HPLC-MS method for use in TDM, in accordance with FDA and EMA guidelines. The optimized protein precipitation protocol required 50 μL of plasma, while chromatographic analysis could be performed in 12 min/sample. This method fulfilled the guidelines requirements and then, it was applied for routine DBV TDM in patients receiving off-label high doses (two 1500 + 1500 mg weekly infusions instead of 1000 + 500 mg), with normal renal function or undergoing hemodialysis: continuous hemodiafiltration caused a relevant reduction in DBV exposure, while intermittent dialysis showed comparable DBV concentrations with those of patients with normal renal function. This confirmed the eligibility of the presented method for use in TDM and its usefulness in clinical practice.