A sensitive liquid chromatography and mass spectrometry method for the determination of posaconazole in human plasma

J Pharm Biomed Anal. 2007 Jan 4;43(1):228-36. doi: 10.1016/j.jpba.2006.06.011. Epub 2006 Jul 21.


Posaconazole is a novel extended-spectrum triazole that has favorable in vitro, in vivo and clinical activity against a number of yeasts and moulds. Posaconazole is available as an oral suspension. The dosage found to result in monitored plasma levels that correlate with clinical evidence of good antifungal activity is 800 mg/day in divided doses. A liquid chromatographic/mass spectrometric method (LC-MS/MS) that can be used by clinicians wishing to quantitate, and thereby monitor, plasma levels of posaconazole in certain patients was validated. The method utilized semi-automated 96-well protein precipitation with gradient chromatographic separation of analytes using a Varian Polaris C-18A (2.0 mm x 50 mm, 5-microm particle size) column. The approximate retention time of posaconazole was 2.0 min. Analytes were detected by using tandem mass spectrometry. Sample introduction and ionization was performed by atmospheric pressure chemical ionization in the positive-ion mode. This method has been proven suitable for routine quantitation of posaconazole over the concentration range of 5.00-5000 ng/mL. Inter-run precision based on percent relative deviation for replicate quality controls was < or = 6.2%. Inter-run accuracy expressed as %DIFF was +/-4.0%. Posaconazole quality controls were stable in human plasma for up to five freeze-thaw cycles, when frozen at -20 degrees C for at least 105 days and when kept at room temperature for 24 h. The lower limit of quantitation was 5.00 ng/mL for a 100-microL sample aliquot. These data indicate that the LC-MS/MS method described is suitable for the rapid measurement of posaconazole over the concentration range of 5.00-5000 ng/mL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antifungal Agents / blood*
  • Calibration
  • Chromatography, High Pressure Liquid
  • Humans
  • Indicators and Reagents
  • Mass Spectrometry
  • Quality Control
  • Reference Standards
  • Reproducibility of Results
  • Solutions
  • Triazoles / blood*


  • Antifungal Agents
  • Indicators and Reagents
  • Solutions
  • Triazoles
  • posaconazole