HPLC analysis of the antifungal agent posaconazole in patients with haematological diseases.
Posaconazole is a new antifungal drug used in prophylaxis and therapy of fungal infections in patients with immunodeficiency. In the clinical development, posaconazole exhibits variable oral bioavailability. Hence drug monitoring is recommended. For this purpose, a rapid and a convenient high-performance liquid chromatography (HPLC) method has been developed. To 200 mul serum, 50 mul internal standard (itraconazole) was added. After precipitation of the proteins with acetonitrile, the clear supernatant was evaporated in a centrifugal evaporator, and the residue was dissolved in the HPLC elution. Separation was done on a chromatography performed by injecting a 50 mul aliquot of the resuspended sample onto a Multohyp C18 BDS column (250 x 4 mm). Column temperature was maintained at 50 degrees C. The flow rate was 1 ml min(-1). Retention time of posaconazole was about 9 min and those of itraconazole was 17 min. The limit of quantification was 50 mug l(-1) and the limit of detection about 10 mug l(-1). Until now the concentration of posaconazole was measured in 14 patients (64 samples). After a daily dosage of 600-800 mg posaconazole the serum concentrations varied between 100 and 3000 mug l(-1) (582 +/- 579 mug l(-1)). Oral bioavailability was especially low in patients with cytostatic therapy and/or bone marrow transplantation. Further studies are needed to establish the therapeutic range of the posaconazole concentrations.
Müller
Carsten
C
Department of Pharmacology, University Hospital Cologne, Cologne, Germany. c.mueller@uni-koeln.de
Arndt
Margit
M
Queckenberg
Christian
C
Cornely
Oliver A
OA
Theisohn
Martin
M
D000935:Antifungal Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016903:Drug Monitoring / Q000379:methods*; D006402:Hematologic Diseases / Q000150:complications*; D006801:Humans; D009181:Mycoses / Q000517:prevention & control; D014230:Triazoles / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics
D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole