Blaich, Cornelia, Mueller, Carsten, Michels, Guido and Wiesen, Martin H. J. (2015). Multi-analyte analysis of non-vitamin K antagonist oral anticoagulants in human plasma using tandem mass spectrometry. Clin. Chem. Lab. Med., 53 (12). S. 1981 - 1991. BERLIN: WALTER DE GRUYTER GMBH. ISSN 1437-4331

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Abstract

Background: The non-vitamin K antagonist oral anticoagulants (NOACs) apixaban, dabigatran, and rivaroxaban are being administered in fixed doses without routine monitoring of anticoagulant activities. Despite this key advantage over vitamin K antagonists (VKAs), assessment of anticoagulant intensities is required in various clinical circumstances. We developed a multi-analyte approach for mass spectrometric analysis of NOACs in human plasma. Methods: Plasma samples were precipitated with acetonitrile. Separation was achieved by liquid chromatography using a C18 column and a gradient elution within a run time of 2.5 min. Positive electrospray ionization was used and ion transitions monitored by a triple quadrupole mass spectrometer. Stable-isotope-labeled analogues of analytes were employed as internal standards for quantitative analysis. Certified external quality control samples were obtained for external validation. Results: For all analytes, linearity could be demonstrated over the concentration range of 1-500 mu g/L (R-2>0.999), and the calculated limits of quantification were <1 mu g/L. Results for inter-and intra-day assay precision and trueness were obtained using internal quality control samples and remained within the acceptance criterion of +/- 15%. External quality control samples were measured at the specified nominal values with inter-and intra-day precisions <14%. Matrix effects were fully compensated by co-eluting internal standards, which in turn did not relevantly influence ionization efficiency. Conclusions: The method enables rapid and reliable simultaneous determination of NOAC concentrations in human plasma. It was successfully introduced into clinical practice; a case with rivaroxaban overdose is presented to exemplify the method's applicability.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Blaich, CorneliaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mueller, CarstenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Michels, GuidoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wiesen, Martin H. J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-388209
DOI: 10.1515/cclm-2014-1108
Journal or Publication Title: Clin. Chem. Lab. Med.
Volume: 53
Number: 12
Page Range: S. 1981 - 1991
Date: 2015
Publisher: WALTER DE GRUYTER GMBH
Place of Publication: BERLIN
ISSN: 1437-4331
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
PERFORMANCE LIQUID-CHROMATOGRAPHY; FACTOR-XA INHIBITOR; PRACTICAL CONSIDERATIONS; ELECTROSPRAY-IONIZATION; CHEMICAL-IONIZATION; COAGULATION ASSAYS; ION SUPPRESSION; UPLC-MS/MS; LC-MS/MS; RIVAROXABANMultiple languages
Medical Laboratory TechnologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/38820

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