Please use this identifier to cite or link to this item: doi:10.22028/D291-31018
Notice: temporarily not accessible for legal reasons
Title: Method development for quantitative determination of seven statins including four active metabolites by means of high-resolution tandem mass spectrometry applicable for adherence testing and therapeutic drug monitoring
Author(s): Wagmann, Lea
Hemmer, Selina
Caspar, Achim T.
Meyer, Markus
Language: English
Title: Clinical Chemistry and Laboratory Medicine
Volume: 58
Issue: 5
Pages: 664-672
Publisher/Platform: De Gruyter
Year of Publication: 2019
Free key words: adherence monitoring
cardiovascular diseases
HMG-CoA reductase inhibitors
DDC notations: 500 Science
540 Chemistry
570 Life sciences, biology
Publikation type: Journal Article
Abstract: Background: Statins are used to treat and prevent cardiovascular diseases (CVDs) by reducing the total serum cholesterol concentration. Unfortunately, dose-related side effects and sub-optimal response, attributed to non-adherence amongst others, were described. Therefore, a fast and sensitive liquid chromatography-high-resolution tandem mass spectrometry (LC-HRMS/MS) method for adherence testing and therapeutic drug monitoring of all currently marketed statins and their active metabolites in human blood plasma should be developed, validated and tested for applicability. Methods:Atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin, as well as ortho- and para-hydroxy-atorvastatin, lovastatin hydroxy acid and simvastatin hydroxy acid were included and several internal standards (IS) tested. Validation was performed according to the guideline of the European Medicines Agency including selectivity, carry-over, accuracy, precision, matrix effects, dilution integrity and analyte stability. Finally, applicability was tested using 14 patient samples submitted for regular toxicological analysis. Results: Due to an analytical interference of atorvastatin-d5, diazepam-d5 and pentobarbital-d5 were chosen as IS for positive and negative ionization mode, respectively. All statins and metabolites fulfilled the validation acceptance criteria except for fluvastatin, which could not be quantified reliably and reproducibly, most probably due to instability. Analyses of human plasma samples revealed concentrations of statins and metabolites below the reference plasma concentrations in the case of eight patients. However, nothing was known concerning patients’ adherence and time between intake and sampling. Conclusions: An LC-HRMS/MS method for identification and quantification of atorvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin and four active metabolites was successfully developed and applicability demonstrated.
DOI of the first publication: 10.1515/cclm-2019-0763
Link to this record: urn:nbn:de:bsz:291--ds-310183
ISSN: 1437-4331
Date of registration: 5-Jun-2020
Faculty: M - Medizinische Fakultät
Department: M - Experimentelle und Klinische Pharmakologie und Toxikologie
Professorship: M - Prof. Dr. Markus Meyer
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

Files for this record:
File Description SizeFormat 
Method development for quantitative determination.pdfPublished Article226,44 kBAdobe PDFView/Open

Items in SciDok are protected by copyright, with all rights reserved, unless otherwise indicated.