UHPLC-MS/MS assay for simultaneous determination of amlodipine, metoprolol, pravastatin, rosuvastatin, atorvastatin with its active metabolites in human plasma, for population-scale drug-drug interactions studies in people living with HIV.

Détails

ID Serval
serval:BIB_00B59FADA800
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
UHPLC-MS/MS assay for simultaneous determination of amlodipine, metoprolol, pravastatin, rosuvastatin, atorvastatin with its active metabolites in human plasma, for population-scale drug-drug interactions studies in people living with HIV.
Périodique
Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
Auteur(s)
Courlet P., Spaggiari D., Desfontaine V., Cavassini M., Alves Saldanha S., Buclin T., Marzolini C., Csajka C., Decosterd L.A.
ISSN
1873-376X (Electronic)
ISSN-L
1570-0232
Statut éditorial
Publié
Date de publication
01/09/2019
Peer-reviewed
Oui
Volume
1125
Pages
121733
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
Thanks to highly active antiretroviral treatments, HIV infection is now considered as a chronic condition. Consequently, people living with HIV (PLWH) live longer and encounter more age-related chronic co-morbidities, notably cardiovascular diseases, leading to polypharmacy. As the management of drug-drug interactions (DDIs) constitutes a key aspect of the care of PLWH, the magnitude of pharmacokinetic DDIs between cardiovascular and anti-HIV drugs needs to be more thoroughly characterized. To that endeavour, an UHPLC-MS/MS bioanalytical method has been developed for the simultaneous determination in human plasma of amlodipine, metoprolol, pravastatin, rosuvastatin, atorvastatin and its active metabolites. Plasma samples were subjected to protein precipitation with methanol, followed by evaporation at room temperature under nitrogen of the supernatant, allowing to attain measurable plasma concentrations down to sub-nanogram per milliliter levels. Stable isotope-labelled analytes were used as internal standards. The five drugs and two metabolites were analyzed using a 6-min liquid chromatographic run coupled to electrospray triple quadrupole mass spectrometry detection. The method was validated over the clinically relevant concentrations ranging from 0.3 to 480 ng/mL for amlodipine, atorvastatin and p-OH-atorvastatin, and 0.4 to 480 ng/mL for pravastatin, 0.5 to 480 ng/mL for rosuvastatin and o-OH-atorvastatin, and 3 to 4800 ng/mL for metoprolol. Validation performances such as trueness (95.4-110.8%), repeatability (1.5-13.4%) and intermediate precision (3.6-14.5%) were in agreement with current international recommendations. Accuracy profiles (total error approach) were lying within the limits of ±30% accepted in bioanalysis. This rapid and robust UHPLC-MS/MS assay allows the simultaneous quantification in plasma of the major currently used cardiovascular drugs and offers an efficient analytical tool for clinical pharmacokinetics as well as DDIs studies.
Mots-clé
Amlodipine/blood, Amlodipine/chemistry, Amlodipine/metabolism, Amlodipine/pharmacokinetics, Anti-HIV Agents/pharmacokinetics, Anti-HIV Agents/therapeutic use, Atorvastatin/blood, Atorvastatin/chemistry, Atorvastatin/metabolism, Atorvastatin/pharmacokinetics, Chromatography, High Pressure Liquid/methods, Drug Interactions, HIV Infections/drug therapy, HIV Infections/metabolism, Humans, Linear Models, Metoprolol/blood, Metoprolol/chemistry, Metoprolol/metabolism, Metoprolol/pharmacokinetics, Pravastatin/blood, Pravastatin/chemistry, Pravastatin/metabolism, Pravastatin/pharmacokinetics, Reproducibility of Results, Rosuvastatin Calcium/blood, Rosuvastatin Calcium/chemistry, Rosuvastatin Calcium/metabolism, Rosuvastatin Calcium/pharmacokinetics, Sensitivity and Specificity, Tandem Mass Spectrometry/methods
Pubmed
Web of science
Création de la notice
18/08/2019 15:00
Dernière modification de la notice
04/01/2020 6:17
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