1. 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.
- Author
-
Courlet P, Spaggiari D, Desfontaine V, Cavassini M, Alves Saldanha S, Buclin T, Marzolini C, Csajka C, and Decosterd LA
- Subjects
- Amlodipine chemistry, Amlodipine metabolism, Amlodipine pharmacokinetics, Anti-HIV Agents pharmacokinetics, Anti-HIV Agents therapeutic use, Atorvastatin chemistry, Atorvastatin metabolism, Atorvastatin pharmacokinetics, Chromatography, High Pressure Liquid methods, Drug Interactions, Humans, Linear Models, Metoprolol chemistry, Metoprolol metabolism, Metoprolol pharmacokinetics, Pravastatin chemistry, Pravastatin metabolism, Pravastatin pharmacokinetics, Reproducibility of Results, Rosuvastatin Calcium chemistry, Rosuvastatin Calcium metabolism, Rosuvastatin Calcium pharmacokinetics, Sensitivity and Specificity, Tandem Mass Spectrometry methods, Amlodipine blood, Atorvastatin blood, HIV Infections drug therapy, HIV Infections metabolism, Metoprolol blood, Pravastatin blood, Rosuvastatin Calcium blood
- Abstract
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.
- Published
- 2019
- Full Text
- View/download PDF