Screening of cardiovascular agents in plasma with LC-MS/MS: A valuable tool for objective drug adherence assessment

A.M. Punt*, N A Stienstra, M E A van Kleef, M Lafeber, W Spiering, P J Blankestijn, M L Bots, E M van Maarseveen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Scopus)
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Adherence to cardiovascular preventive agents is important to prevent short and long term cardiovascular events. Recently, qualitatively compound screening using liquid chromatography-tandem mass spectrometry (LC-MS/MS) has gained interest for drug adherence assessment in patients at high risk of cardiovascular events. Therefore, we developed and tested an assay including 52 compounds and metabolites, covering over 95% of the antihypertensive and antithrombotic agents available worldwide. Trichloroacetic acid was used as simple and fast method for protein precipitation. The assay was validated for lower limit of quantification (LLOQ), linearity, stability for freeze/thaw, room temperature, autosampler and matrix effects. The LLOQ for each compound was targeted under the population trough concentration (PTC) as reported in literature to assure high sensitivity for adherence detection. This was accomplished for 50 of 52 compounds with a LLOQ equal or lower compared to the PTC. Linearity was confirmed for all compounds (r2 > 0.995), except for acetylsalicylic acid (r2 = 0.991). For room temperature stability, 12 compounds showed degradation over 20% after 20 h. 3 compounds suffer from matrix effect with recoveries < 50%. After analytical validation, blood samples from 91 patients with difficult-to-treat hypertension were analyzed. Patients were unaware of adherence assessment. Adherence varied largely per agent and per concentration ratio (CR) (ratio of the detected concentration with LC-MS/MS and the PTC) cut-off value. Additionally, stratification by adherence group showed that the percentage of patients classified as non-adherent increased from 6.6% for qualitative analysis (pos/neg) to 19.8% for a CR cut-off of 0.5. The data imply that using the CR cut off values has a significant and relevant effect on patient adherence classification.

Original languageEnglish
Pages (from-to)103-110
Number of pages8
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Early online date27 May 2019
Publication statusPublished - 15 Jul 2019
Externally publishedYes

Bibliographical note

Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.


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