A simple and sensitive liquid chromatography-tandem mass spectrometry (LC– MS/MS) method has been developed for the simultaneous determination of atorvastatin (ATOR), ezetimibe (EZM) and their three metabolites including o-hydroxyl atorvastatin (o-OH ATOR), p-hydroxyl atorvastatin (p-OH ATOR), and ezetimibe-glucuronide (EZM-G) in human plasma using benzyl paraben (BP) as internal standard (IS). The analytes and IS were ionized using ESI positive ion mode (ATOR, o-OH ATOR, and p-OH ATOR), ESI negative ion mode (EZM, EZM-G, and BP), and operated in multiple reaction monitoring (MRM) mode. They were next extracted by salting-out assisted liquid–liquid extraction with acetonitrile, and then analyzed by liquid chromatography on a reversed-phase chromatographic column (50 mm × 4.6 mm; 3.5 µm), using a mixture of ac-etonitrile and an acetic acid solution (0.5%) as the mobile phase, showing high extraction effi-ciency (>70%), and a minimized matrix effect. The method was satisfactorily validated, and showed excellent linearity over wide concentration ranges of 0.06–15 ng/mL, 0.6–150 ng/mL, 0.4–100 ng/mL, 0.12–30 ng/mL, and 0.05–3 ng/mL for EZM, EZM-G, ATOR, o-OH ATOR, and p-OH ATOR, respectively.

Reducing levels of low-density-lipoprotein-cholesterol (LDL-C) below recommended thresholds is a core component of cardiovascular prevention strategies. We hypothesized that the addition of bempedoic acid to patients already on statin-ezetimibe therapy was more effective than titrating the statin dose in reducing LDL-C. The study enrolled 120 patients at high cardiovascular risk, and with LDL-C above 70 mg/dl. They were randomly divided in two groups: bempedoic acid (BA) group, taking bempedoic acid in addition to statin plus ezitimibe, and the statin titration (ST) group including patients who doubled the dose of statin. At 12-weeks, BA group presented a greater significant decrease of LDL-C compared to ST group (-22.9% vs 7.5% p 0.002). Total-cholesterol decreased significantly in the BA group compared to ST (-14.8% vs-4.7% ; p 0.013) No significant between-groups changes in HDL and triglycerides occurred. At 12 weeks the number of patients who reached LDL-C lower than 70 mg/dl was 38 (63%) in the BA group versus 22 (37%) in the ST group (between group p 0.034). In the BA group the LDL lowering effect of bempedoic acid was similar between patients taking atorvastatin and rosuvastatin. No side effects occurred during the follow up period. In conclusion, the addition of Bempedoic acid to statin/ezetimibe combined treatment was more effective than doubling the dose of statin in reducing LDL-C. levels and increased the number of patients reaching the LDL-C goal.

A brown seaweed consumed worldwide, Fucus vesiculosus, has been used to prevent atherosclerosis and hypercholesterolemia, among other uses, however, the mechanisms of action that lead to these effects are not yet fully understood. An F. vesiculosus aqueous extract, prepared as a soup was characterized as rich in sev-eral bioactive compounds, mainly phlorotannin and peptides. This work aims to study the in vitro effect of this extract on the expression of different proteins involved in the synthesis and transport of cholesterol in HepG2 cells, though a proteomic analysis, western blot and qRT-PCR. The results demonstrated that, in liver cells, the extract decreases the expression of 4 proteins involved in cholesterol biosynthesis process and also decrease the expression of two important transporters proteins of cholesterol, NPC1L1 and ABCG5, as well as decrease the NPC1L1 mRNA levels. Our study demonstrates some mechanisms of action of bioactive com-pounds from F. vesiculosus that may explain its previously reported hypocholesterolemic effect.