Quantification of 21 antihypertensive drugs in serum using UHPLC-MS/MS
Autor: | Solfrid Hegstad, Per Ole M. Gundersen, Olav Spigset, Arne Helland |
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Rok vydání: | 2018 |
Předmět: |
Serum
medicine.drug_class Adrenergic beta-Antagonists Clinical Biochemistry Angiotensin-Converting Enzyme Inhibitors 030204 cardiovascular system & hematology 01 natural sciences Biochemistry High-performance liquid chromatography Analytical Chemistry Angiotensin Receptor Antagonists 03 medical and health sciences 0302 clinical medicine Hydrochlorothiazide Irbesartan Limit of Detection Tandem Mass Spectrometry Liquid chromatography–mass spectrometry medicine Humans Bendroflumethiazide Diuretics Antihypertensive drug Adrenergic alpha-Antagonists Antihypertensive Agents Chromatography High Pressure Liquid Chromatography medicine.diagnostic_test Chemistry 010401 analytical chemistry Reproducibility of Results Cell Biology General Medicine Calcium Channel Blockers Atenolol 0104 chemical sciences Therapeutic drug monitoring Calibration Metabolome Drug Monitoring medicine.drug |
Zdroj: | Journal of Chromatography B. 1089:84-93 |
ISSN: | 1570-0232 |
Popis: | Background Poor drug adherence in hypertensive patients can lead to treatment failure and increased cardiovascular morbidity, as well as increased costs to society. An analytical method based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MSMS) was developed and validated for use in routine therapeutic drug monitoring (TDM). The method includes 21 antihypertensive drugs or active metabolites from the groups beta blockers (n=5), calcium antagonists (n=5), angiotensin II receptor antagonists (n=4), angiotensin converting enzyme (ACE) inhibitors (n=3) and diuretics (n = 3), in addition to one α1-selective alpha blocker. Method A 200 µL serum sample was handled automatically using a pipetting robot. Protein precipitation was performed with 600 µL of 1% formic acid in acetonitrile (v:v) and phospholipid removal was carried out using a Waters OSTRO™ 96-well plate. After evaporation and reconstitution the eluent was injected thrice with different inlet and mass spectrometric methods to cover the different physico-chemical properties of the drugs and the variations in therapeutic concentration ranges between drugs. Acquity UPLC BEH C18 (2.1x50mm, 1.7 µm) column equipped with a corresponding pre-column was used for chromatographic separation. For every analyte an isotopically labelled analogue served as internal standard, except for lisinopril where enalaprilat-d5 was used. Results Accuracies were in the range of -13.7 to 13.2% and intra-day and inter-day precisions in the range of 1.1 to 10.5%. The linearity within the calibration ranges expressed as coefficient of determination was higher than 0.995 for all compounds. Matrix effects and recovery efficiencies were within acceptable limits. The limits of quantitation varied from 0.02 to 10.7 µg/L. The stability of the drugs in serum at different conditions was tested. Diltiazem was not stable at 4-8 °C with up to 23.5 % loss after six days. Degradation of atenolol, irbesartan, bendroflumethiazide, hydrochlorothiazide and diltiazem was observed when stored at 30 °C. The suitability of the method was demonstrated in a routine TDM setting, analysing samples from 127 patients undergoing antihypertensive drug treatment. |
Databáze: | OpenAIRE |
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