Vitexin and isovitexin are natural flavone C-glucosides that have numerous benefits for human health. However, their low oral bioavailability and poor gastrointestinal absorption dramatically restrict their potential medicinal uses. To overcome this challenge, chitosan-coated alginate microcapsules were prepared for intragastrical administration to rabbits. An LC-MS/MS method was developed and validated for the simultaneous determination of vitexin and isovitexin in the plasma of treated rabbits, using salicylic acid as the internal standard. Raw rabbit plasma samples were deproteinized using acetonitrile as a precipitation agent. Chromatographic separation was performed on a reversed-phase C18 column (100 mm × 4.6 mm, 3.5 µm), with an isocratic mobile solvent system comprising methanol and 0.1% acetic acid (40:60) as the mobile phase. All the analytes and the internal standard were ionized on a triple quadrupole mass spectrometer and electrospray ionization, operating in negative mode and multiple reaction monitoring. The analytical approach developed underwent validation in terms of system suitability, specificity, selectivity, LLOQ of 2 ng/mL, linearity (2.0–200 ng/mL, R² > 0.99), accuracy (the intra- and inter-day from 94 to 110% with the relative standard deviations no more than 8.7%, precision with the recoveries from 97% to 102%, matrix effect (90–100%), carry-over, dilution integrity (2 times), and stability at room and frozen temperature for up to 1 month, and all the parameters met FDA and EMA requirements for bioanalytical methods. The validated procedure was applied to measure the absorption of vitexin and isovitexin from encapsulated extracts in a pilot pharmacokinetic study on rabbit plasma. Compared to the raw traditional extracts, the microcapsules enhanced the bioavailability of vi-texin and isovitexin regarding C_max and AUC values.

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 the 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 then extracted via salting-out assisted liquid–liquid extraction with acetonitrile and analyzed via liquid chromatography on a reversed-phase chromatographic column (50 mm × 4.6 mm; 3.5 µm) using a mixture of acetonitrile and an acetic acid solution (0.5%) as the mobile phase, showing high extraction efficiency (>70%), and a minimized matrix effect. The method was satisfactorily validated, and it 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.

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.