Please use this identifier to cite or link to this item:
doi:10.22028/D291-31018
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 statins TDM |
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 hdl:20.500.11880/29223 http://dx.doi.org/10.22028/D291-31018 |
ISSN: | 1437-4331 1434-6621 |
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 | Size | Format | |
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Method development for quantitative determination.pdf | Published Article | 226,44 kB | Adobe PDF | View/Open |
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