Measurement of warfarin in the oral fluid of patients undergoing anticoagulant oral therapy

PLoS One. 2011;6(12):e28182. doi: 10.1371/journal.pone.0028182. Epub 2011 Dec 2.

Abstract

Background: Patients on warfarin therapy undergo invasive and expensive checks for the coagulability of their blood. No information on coagulation levels is currently available between two controls.

Methodology: A method was developed to determine warfarin in oral fluid by HPLC and fluorimetric detection. The chromatographic separation was performed at room temperature on a C-18 reversed-phase column, 65% PBS and 35% methanol mobile phase, flow rate 0.7 mL/min, injection volume 25 µL, excitation wavelength 310 nm, emission wavelength 400 nm.

Findings: The method was free from interference and matrix effect, linear in the range 0.2-100 ng/mL, with a detection limit of 0.2 ng/mL. Its coefficient of variation was <3% for intra-day measurements and <5% for inter-day measurements. The average concentration of warfarin in the oral fluid of 50 patients was 2.5±1.6 ng/mL (range 0.8-7.6 ng/mL). Dosage was not correlated to INR (r = -0.03, p = 0.85) but positively correlated to warfarin concentration in the oral fluid (r = 0.39, p = 0.006). The correlation between warfarin concentration and pH in the oral fluid (r = 0.37, p = 0.009) confirmed the importance of pH in regulating the drug transfer from blood. A correlation between warfarin concentration in the oral fluid and INR was only found in samples with pH values ≥7.2 (r = 0.84, p = 0.004).

Conclusions: Warfarin diffuses from blood to oral fluid. The method allows to measure its concentration in this matrix and to analyze correlations with INR and other parameters.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Anticoagulants / analysis
  • Anticoagulants / therapeutic use*
  • Blood Coagulation / drug effects
  • Chromatography, High Pressure Liquid / methods
  • Drug Monitoring / methods
  • Female
  • Fluorometry / methods
  • Humans
  • Hydrogen-Ion Concentration
  • International Normalized Ratio
  • Male
  • Middle Aged
  • Principal Component Analysis
  • Reproducibility of Results
  • Saliva / drug effects*
  • Saliva / metabolism
  • Warfarin / analysis
  • Warfarin / therapeutic use*

Substances

  • Anticoagulants
  • Warfarin