dc.contributor.author | Thorstensen, Christian W. | |
dc.contributor.author | Clasen, Per-Erik | |
dc.contributor.author | Rognstad, Stine | |
dc.contributor.author | Haldsrud, Renate | |
dc.contributor.author | Føreid, Siri | |
dc.contributor.author | Helstrøm, Trine | |
dc.contributor.author | Bergland, Ola Undrum | |
dc.contributor.author | Halvorsen, Lene Vernås | |
dc.contributor.author | Aune, Arleen | |
dc.contributor.author | Olsen, Erik | |
dc.contributor.author | Brobak, Karl Marius | |
dc.contributor.author | Høieggen, Aud | |
dc.contributor.author | Gustavsen, Ingebjørg G. | |
dc.contributor.author | Larstorp, Anne Cecilie Kjeldsen | |
dc.contributor.author | Søraas, Camilla Lund | |
dc.contributor.author | Opdal, Mimi Stokke | |
dc.date.accessioned | 2022-10-03T05:09:56Z | |
dc.date.available | 2022-10-03T05:09:56Z | |
dc.date.issued | 2022-06-23 | |
dc.description.abstract | We developed three ultra-high pressure liquid chromatography coupled to mass spectrometry detection (UHPLCMS/MS) methods to quantify 25 antihypertensive drugs in serum samples. Patient-reported drug lists were
collected, and drug concentrations were analysed in samples from 547 patients, half with uncontrolled hypertension, and all treated with ≥ 2 antihypertensive drugs.
For sample preparation, serum was mixed with deuterated internal standards and acetonitrile and precipitated. Aliquots of the supernatant were injected on UHPLC-MSMS with a C18 reversed phase column. The mobile
phase was 0.1 % HCOOH (formic acid) in water and 0.1 % HCOOH in acetonitrile (except in methanol for
spironolactone/canrenone) at a flow rate of 0.4 mL/min. The calibrators and internal controls were prepared in
Autonorm™. The calibration ranges were wide, and the models were linear or quadratic with squared correlation
coefficients ≥ 0.97. The limits of detection and quantification, specificity, carry-over, and matrix effects were
acceptable. The accuracy of the internal controls was in the range 85–121 %, and the intermediate precision for
all drugs was 4–28 %.
The patient-reported antihypertensive drug use and the detected serum drug concentrations were in accordance with that most frequently prescribed nationally. The percent non-detectable level was 5–10 % for bendroflumethiazide, doxazosin, nifedipine, and ramipril. Often the drug dose chosen was lower than the
recommended maximum daily dose. We report the maximum (C<sub>max</sub>) and minimum (C<sub>min</sub>) drug concentrations
after drug intake. The inter-individual pharmacokinetic variability at Cmin was 18-fold for hydrochlorothiazide,
22-fold for losartan carboxyl acid, 26-fold for amlodipine, 44-fold for candesartan, and 50-fold for valsartan.
Our methods are suitable for measuring antihypertensive drugs in patient serum for therapy control. | en_US |
dc.identifier.citation | Thorstensen, Clasen, Rognstad, Haldsrud, Føreid, Helstrøm, Bergland, Halvorsen, Aune, Olsen, Brobak, Høieggen, Gustavsen, Larstorp, Søraas, Opdal. Development of UHPLC-MS/MS methods to quantify 25 antihypertensive drugs in serum in a cohort of patients treated for hypertension. Journal of Pharmaceutical and Biomedical Analysis. 2022;219 | en_US |
dc.identifier.cristinID | FRIDAID 2056774 | |
dc.identifier.doi | 10.1016/j.jpba.2022.114908 | |
dc.identifier.issn | 0731-7085 | |
dc.identifier.issn | 1873-264X | |
dc.identifier.uri | https://hdl.handle.net/10037/26952 | |
dc.language.iso | eng | en_US |
dc.publisher | Elsevier | en_US |
dc.relation.journal | Journal of Pharmaceutical and Biomedical Analysis | |
dc.rights.accessRights | openAccess | en_US |
dc.rights.holder | Copyright 2022 The Author(s) | en_US |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | en_US |
dc.rights | Attribution 4.0 International (CC BY 4.0) | en_US |
dc.title | Development of UHPLC-MS/MS methods to quantify 25 antihypertensive drugs in serum in a cohort of patients treated for hypertension | en_US |
dc.type.version | publishedVersion | en_US |
dc.type | Journal article | en_US |
dc.type | Tidsskriftartikkel | en_US |
dc.type | Peer reviewed | en_US |