A routine method for the quantification of the novel antimycotic drug posaconazole in plasma using liquid chromatography-tandem mass spectrometry

Background: Posaconazole is now widely used for prophylaxis of invasive fungal infections in immunocompromised patients. The pharmacokinetic properties of the drug argue for therapeutic monitoring, but so far described analytical methods have shortcomings with respect to application in a routine setting. The aim of our work was to develop an analytical method suitable for routine use. Methods: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used. For sample preparation, protein precipitation followed by on-line solid phase extraction was used. SCH 56984, a posaconazole related compound provided by the manufacturer of posaconazole, was used as internal standard. Results: The method was characterized by short hands-on time and an analytical run time of four minutes. Validation data demonstrated acceptable analytical performance. Conclusions: LC-MS/MS with on-line solid phase extraction for sample preparation allows the implementation of a convenient and reliable method for pharmacokinetic monitoring of posaconazole. Clin Chem Lab Med 2009;47:579–84.