Quantification of 21 antihypertensive drugs in serum using UHPLC-MS/MS

Autor: Solfrid Hegstad, Per Ole M. Gundersen, Olav Spigset, Arne Helland
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
Externí odkaz: