A LC-MS method to quantify tenofovir urinary concentrations in treated patients

Marco Simiele; Chiara Carcieri; Amedeo De Nicolò; Alessandra Ariaudo; Mauro Sciandra; Andrea Calcagno; Stefano Bonora; Giovanni Di Perri; Antonio D'Avolio

doi:10.1016/j.jpba.2015.05.001

A LC-MS method to quantify tenofovir urinary concentrations in treated patients

J Pharm Biomed Anal. 2015 Oct 10:114:8-11. doi: 10.1016/j.jpba.2015.05.001. Epub 2015 May 8.

Authors

Marco Simiele¹, Chiara Carcieri², Amedeo De Nicolò¹, Alessandra Ariaudo¹, Mauro Sciandra¹, Andrea Calcagno¹, Stefano Bonora¹, Giovanni Di Perri¹, Antonio D'Avolio³

Affiliations

¹ Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Turin 10149, Italy.
² Pharmacy Department, Amedeo di Savoia Hospital of Turin, Turin, Italy.
³ Laboratory of Clinical Pharmacology and Pharmacogenetics, Department of Medical Sciences, University of Turin, Amedeo di Savoia Hospital, Turin 10149, Italy. Electronic address: antonio.davolio@unito.it.

PMID: 25997174
DOI: 10.1016/j.jpba.2015.05.001

Abstract

Tenofovir disoproxil fumarate is a prodrug of tenofovir used in the treatment of HIV and HBV infections: it is the most used antiretroviral worldwide. Tenofovir is nucleotidic HIV reverse trascriptase inhibitor that showed excellent long-term efficacy and tolerability. However renal and bone complications (proximal tubulopathy, hypophosphatemia, decreased bone mineral density, and reduced creatinine clearance) limit its use. Tenofovir renal toxicity has been suggested as the consequence of drug entrapment in proximal tubular cells: measuring tenofovir urinary concentrations may be a proxy of this event and it may be used as predictor of tenofovir side effects. No method is currently available for quantifying tenofovir in this matrix: then, the aim of this work was to validate a new LC-MS method for the quantification of urinary tenofovir. Chromatographic separation was achieved with a gradient (acetonitrile and water with formic acid 0.05%) on an Atlantis 5 μm T3, 4.6 mm × 150 mm, reversed phase analytical column. Detection of tenofovir and internal standard was achieved by electrospray ionization mass spectrometry in the positive ion mode. Calibration ranged from 391 to 100,000 ng/mL. The limit of quantification was 391 ng/mL and the limit of detection was 195 ng/mL. Mean recovery of tenofovir and internal standard were consistent and stable, while matrix effect resulted low and stable. The method was tested on 35 urine samples from HIV-positive patients treated with tenofovir-based HAARTs and did not show any significant interference with antiretrovirals or other concomitantly administered drugs. All the observed concentrations in real samples fitted the calibration range, confirming the capability of this method for the use in clinical routine. Whether confirmed in ad hoc studies this method may be used for quantifying tenofovir urinary concentrations and help managing HIV-positive patients treated with tenofovir.

Keywords: HBV; HIV; Mass spectrometry; TDF; Therapeutic drug monitoring; Urine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antiretroviral Therapy, Highly Active / methods
Calibration
Chromatography
Chromatography, Liquid / methods*
Drug Monitoring / methods
HIV Infections / drug therapy
Hepatitis B / drug therapy
Humans
Limit of Detection
Mass Spectrometry / methods*
Reproducibility of Results
Tenofovir / analysis
Tenofovir / urine*
United States
United States Food and Drug Administration
Urinalysis

Substances

Tenofovir