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

Autor: E.M. van Maarseveen, N.A. Stienstra, Wilko Spiering, Arjen M Punt, Peter J. Blankestijn, M. L. Bots, M E A M Van Kleef, Melvin Lafeber
Přispěvatelé: Internal Medicine, Epidemiology
Rok vydání: 2019
Předmět:
Antihypertensive agents
Clinical Biochemistry
030226 pharmacology & pharmacy
01 natural sciences
Biochemistry
Analytical Chemistry
chemistry.chemical_compound
0302 clinical medicine
Liquid chromatography–mass spectrometry
Limit of Detection
Tandem Mass Spectrometry
Antithrombotic
Trichloroacetic acid
Chromatography
High Pressure Liquid
education.field_of_study
Chromatography
Chemistry
Hypertension/drug therapy
Antihypertensive Agents/blood
General Medicine
Antithrombotic agents
Randomized Controlled Trial
Hypertension
Screening
Drug Monitoring
Drug Monitoring/methods
Population
Tandem Mass Spectrometry/methods
Medication Adherence
03 medical and health sciences
High Pressure Liquid/methods
Journal Article
Protein precipitation
Humans
Trough Concentration
education
Antihypertensive Agents
Detection limit
010401 analytical chemistry
Reproducibility of Results
Cell Biology
Cardiovascular agents
0104 chemical sciences
Adherence
Liquid chromatography-tandem mass spectrometry
Cardiovascular agent
Linear Models
Chromatography
High Pressure Liquid/methods
Zdroj: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 1121, 103-110. Elsevier
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 1121, 103. Elsevier
ISSN: 1873-376X
1570-0232
Popis: 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.
Databáze: OpenAIRE
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