Development and validation of a UPLC-MS/MS method for simultaneous quantification of levofloxacin, ciprofloxacin, moxifloxacin and rifampicin in human plasma: Application to the therapeutic drug monitoring in osteoarticular infections

J Pharm Biomed Anal. 2020 May 10:183:113137. doi: 10.1016/j.jpba.2020.113137. Epub 2020 Feb 1.

Abstract

Background: Fluoroquinolones and rifampicin are antibiotics frequently used for the treatment of osteoarticular infections, and their therapeutic drug monitoring is recommended. The aim of this study was to develop and validate a rapid and selective method of simultaneous quantification of levofloxacin, ciprofloxacin, moxifloxacin and rifampicin with short pretreatment and run times in order to be easily used in clinical practice.

Methods: After a simple protein precipitation of plasma samples, the chromatographic separation was performed using an ultra-performance liquid chromatography system coupled with mass tandem spectrometry in a positive ionization mode. The mobile phase consisted of a gradient elution of water-formic acid (100:0.1, v/v)-ammonium acetate 2 mM (A) and methanol-formic acid (100:0.1, v/v)-ammonium acetate 2 mM (B) at a flow rate at 0.3 mL/min.

Results: Analysis time was 5 min per run, and all analytes and internal standards eluted within 0.85-1.69 minutes. The calibration curves were linear over the range from 0.5-30 μg/mL for levofloxacin, ciprofloxacin, moxifloxacin and rifampicin with linear regression coefficients above 0.995 for all analytes. The intra-day and inter-day coefficients of variation were below 10 % for lower and higher concentration. This method was successfully applied to drug monitoring in patients with an osteoarticular infection.

Conclusion: A simple, rapid, and selective liquid chromatography-tandem mass spectrometry method was developed and validated for the simultaneous quantification of levofloxacin, ciprofloxacin, moxifloxacin and rifampicin in human plasma.

Keywords: Antibiotics; Liquid chromatography; Mass spectrometry; Osteoarticular infections; Therapeutic drug monitoring.

MeSH terms

  • Chromatography, High Pressure Liquid / methods*
  • Ciprofloxacin / blood*
  • Drug Monitoring / methods
  • Female
  • Humans
  • Levofloxacin / blood*
  • Limit of Detection
  • Male
  • Middle Aged
  • Moxifloxacin / blood*
  • Plasma / chemistry*
  • Reproducibility of Results
  • Rifampin / blood*
  • Tandem Mass Spectrometry / methods*

Substances

  • Ciprofloxacin
  • Levofloxacin
  • Moxifloxacin
  • Rifampin