Universität zu Köln

Mueller, Carsten, Gehlen, David, Blaich, Cornelia, Prozeller, Domenik, Liss, Blasius, Streichert, Thomas and Wiesen, Martin H. J. (2017). Reliable and Easy-To-Use Liquid Chromatography-Tandem Mass Spectrometry Method for Simultaneous Analysis of Fluconazole, Isavuconazole, Itraconazole, Hydroxy-Itraconazole, Posaconazole, and Voriconazole in Human Plasma and Serum. Ther. Drug Monit., 39 (5). S. 505 - 514. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 1536-3694

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Abstract

Background: A fast and easy-to-use liquid chromatographytandem mass spectrometry method for the determination and quantification of 6 triazoles [fluconazole (FLZ), isavuconazole (ISZ), itraconazole (ITZ), hydroxy-itraconazole (OH-ITZ), posaconazole (PSZ), and voriconazole (VRZ)] in human plasma and serum was developed and validated for therapeutic drug monitoring. Methods: Sample preparation was based on protein precipitation with acetonitrile and subsequent centrifugation. Isotope-labeled analogues for each analyte were used as internal standards. Chromatographic separation was achieved using a 50 u 2.1 mm, 1.9 mm polar Hypersil Gold C18 column and mobile phase consisting of 0.1% formic acid/acetonitrile (45%/55%, vol/vol) at a flow rate of 340 mu L/min. The triazoles were simultaneously detected using a triple-stage quadrupole mass spectrometer operated in selected reaction monitoring mode with positive heated electrospray ionization within a single runtime of t = 3.00 minutes. Results: Linearity of all azole concentration ranges was verified by the Mandel test and demonstrated for all azoles. All calibration curves were linear and fitted using least squares regression with a weighting factor of the reciprocal concentration. Limits of detection (mu g/L/L) were FLZ, 9.3; ISZ, 0.3; ITZ, 0.6; OH-ITZ, 8.6; PSZ, 3.4; and VRZ, 2.1. The lower limits of quantitation (mu g/L/liter) were FLZ, 28.3; ISZ, 1.0; ITZ, 1.7; OH-ITZ, 26.2; PSZ, 10.3; and VRZ, 6.3. Intraday and interday precisions ranged from 0.6% to 6.6% for all azoles. Intraday and interday accuracies (% bias) of all analytes were within 10.5%. In addition, we report on a 29-year-old white woman (94 kg body weight) with a history of acute myeloid leukemia who underwent stem cell transplantation. Because of diagnosis of aspergillus pneumonia, antifungal pharmacotherapy was initiated with different application modes and dosages of ISZ, and plasma concentrations were monitored over a time period of 6 months. Conclusions: A precise and highly sensitive liquid chromatographytandem mass spectrometry method was developed that enables quantification of triazoles in plasma and serum matrix across therapeutically relevant concentration ranges. It was successfully implemented in our therapeutic drug monitoring routine service and is suitable for routine monitoring of antifungal therapy and in severely ill patients.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mueller, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Gehlen, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Blaich, Cornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Prozeller, Domenik UNSPECIFIED UNSPECIFIED UNSPECIFIED Liss, Blasius UNSPECIFIED UNSPECIFIED UNSPECIFIED Streichert, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Wiesen, Martin H. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-217022
Journal or Publication Title:	Ther. Drug Monit.
Volume:	39
Number:	5
Page Range:	S. 505 - 514
Date:	2017
Publisher:	LIPPINCOTT WILLIAMS & WILKINS
Place of Publication:	PHILADELPHIA
ISSN:	1536-3694
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LC-MS/MS METHOD; AZOLE ANTIFUNGAL DRUGS; SIMULTANEOUS QUANTIFICATION; TRIAZOLE ANTIFUNGALS; HYDROXYITRACONAZOLE; QUANTITATION; PROPHYLAXIS; GUIDELINES; PHARMACOKINETICS; ASPERGILLOSIS Multiple languages Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21702