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Caspofungin (MK-0991; L-743,872) is the first representative of a new important class of antifungal agents, the glucan synthesis inhibitors. To the authors' best knowledge, to date only one high-performance liquid chromatography (HPLC) method has been published for the determination of caspofungin in serum. Severe difficulties with sorption were described. We developed a new method which addresses these difficulties using an advanced column-switching technique for fully automated analysis of caspofungin in serum without any pre-treatment. Extraction was performed automatically inline, using a diol column, followed by chromatography on a CN column. Detection was performed by electrospray ionisation tandem mass spectrometry (ESI-MS/MS) with isolation and fragmentation in the positive ion mode. Total analysis time was 30 min. Detection of caspofungin was achieved by retention time, isolation and fragmentation of the double positively charged caspofungin ion. This LC/MS assay was validated for between-run accuracy (max. 110%) and precision (max. CV 16.1%). The lower limit of quantification was 0.2 microg/mL. The analytical method with fully automated inline extraction of caspofungin described here removes the need for difficult and time-consuming sample pre-treatment. Sorption of caspofungin is not of importance. Additional advantages of the new method are that only a small quantity of serum (5 microL) is needed and that the method is very specific.

A sensitive and rapid HPLC assay for the determination of fluconazole in serum is described. HPLC-integrated sample preparation allows direct injection of serum samples without any pretreatment. The in-line extraction technique is carried out by automatically switching from the extraction column (Lichrospher ADS C8) to the analytic column (Nucleosil C18). After 6 minutes the matrix passes the extraction column, and the retained analyte is quantitatively transferred to the analytic column, where separation by isocratic HPLC is performed. The extraction eluent is sodium dihydrogen phosphate buffer, pH 5.0 (50 mM), and the analytic eluent is acetonitrile/sodium dihydrogen phosphate buffer, pH 5.0 (50 mM) (26.8/73.2, vol/vol). Fluconazole is detected according to its absorption maximum at 210 nm. The lower limit of quantification (LLOQ) is 0.65 microg/mL, the limit of detection (LOD) is 0.2 microg/mL, and the quantification range is 0.65-23.3 microg/mL. The assay was precise with a between-run coefficient of variation of < or = 5.59%. The within-run accuracy was 99.8% and 103.4%, and the between-run accuracy was 99.2% and 99.7%, respectively, for the concentrations 23.3 microg/mL and 1.3 microg/mL. The recovery was 78%. The described procedure allows sample cleanup and determination within 20 minutes, thereby facilitating drug monitoring in clinical routine. The method was applied successfully.

The results of this study suggest, that Unacid is an effective antibiotic in the prophylaxis of ORN in irradiated patients with head and neck tumors.