Universität zu Köln

Wiesena, Martin H. J., Blaich, Cornelia, Streichert, Thomas, Michels, Guido and Mueller, Carsten (2017). Paramagnetic micro-particles as a tool for rapid quantification of apixaban, dabigatran, edoxaban and rivaroxaban in human plasma by UHPLC-MS/MS. Clin. Chem. Lab. Med., 55 (9). S. 1349 - 1360. BERLIN: WALTER DE GRUYTER GMBH. ISSN 1437-4331

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Abstract

Background: Assessment of the anticoagulant activity of direct oral anticoagulants (DOACs) is justified in special clinical situations. Here, we evaluated two independent extraction methods and developed a multi-analyte ultra-high performance liquid chromatography tandem mass (UHPLC-MS/MS) method for the quantification of apixaban, dabigatran, edoxaban and rivaroxaban in human plasma. Methods: Routine extraction based on protein precipitation with acetonitrile and subsequent centrifugation was compared to sample clean-up using commercial paramagnetic micro-particles and subsequent magnetic depletion. Stable isotope-labeled analogs of all analytes were employed as internal standards. The method was validated according to international guidelines in terms of linearity, precision, trueness, sensitivity, recovery and matrix effects. The performances of both extraction methods were assessed in clinical samples obtained from patients treated with either apixaban or rivaroxaban. Additionally, we report on a patient with nonadherence to rivaroxaban treatment and fulminant pulmonary embolism. Results: The method was linear from 2 to 500 ng/mL for all analytes, and quantification of DOACs was established within a run time of 2.0 min. Based on MS/MS analyte responses, relative matrix effects were better controlled for dabigatran after extraction with paramagnetic micro-particles. Internal standards fully compensated for recovery and matrix effects in all assays, yielding equivalent results for both methods. Apixaban and rivaroxaban concentrations determined in clinical samples after extraction with both methods were in good agreement (R-2 = 0.990). Conclusions: A rapid and accurate multi-component UHPLC-MS/MS method for the quantification of four DOACs in human plasma was established. Paramagnetic micro-particles appear suitable for clean-up of plasma samples for LC-MS/MS-based therapeutic drug monitoring purposes.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Wiesena, Martin H. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Blaich, Cornelia UNSPECIFIED UNSPECIFIED UNSPECIFIED Streichert, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Michels, Guido UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Carsten UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-221225
DOI:	10.1515/cclm-2016-0888
Journal or Publication Title:	Clin. Chem. Lab. Med.
Volume:	55
Number:	9
Page Range:	S. 1349 - 1360
Date:	2017
Publisher:	WALTER DE GRUYTER GMBH
Place of Publication:	BERLIN
ISSN:	1437-4331
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PERFORMANCE LIQUID-CHROMATOGRAPHY; TANDEM MASS-SPECTROMETRY; FACTOR XA INHIBITOR; ANTAGONIST ORAL ANTICOAGULANTS; COAGULATION ASSAYS; SAMPLE PREPARATION; LABORATORY MEASUREMENT; CLINICAL-EVALUATION; PHARMACOKINETICS; DEPROTEINATION Multiple languages Medical Laboratory Technology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22122