Electrospray ionization collision-induced dissociation tandem mass spectrometry of amoxicillin and ampicillin and their degradation products.

RATIONALE: Detailed analysis of the literature results on the electrospray ionization mass spectrometry (ESI-MS) fragmentation of amoxicillin and ampicillin, and their comparison with our results, have revealed some incorrect suggestions or incomplete interpretations of mass spectra of these compounds. Therefore, this paper contains a comprehensive discussion devoted to the ESI-MS/MS of ampicillin and amoxicillin as well as their degradation products, namely products of hydrolysis and methanolysis. METHODS: Electrospray ionization collision-induced dissociation tandem mass (ESI-CID-MS/MS) spectra and accurate mass measurements were made on a quadrupole time-of-flight (Q-tof) mass spectrometer. Hydrolysis of the antibiotics was performed by heating, for a few hours, their aqueous solutions adjusted to pH 10. Methanolysis of the antibiotics was performed by heating their methanol solutions for a few minutes. Additionally, mass spectra of isotope-labeled compounds were also obtained. RESULTS: A number of fragment ions, previously wrongly interpreted or not interpreted, have been rationalized. For example, formation of an abundant fragment at m/z 208 originating from the protonated amoxicillin molecule (ion [Amox + H](+)) was previously rationalized as a result of breaking of two bonds of the ß-lactam ring. We found that this fragment ion had to be formed by the loss of ammonia and breaking of three bonds of the bicyclic system. CONCLUSIONS: The discussion presented enables a better understanding of the MS decompositions of amoxicillin and ampicillin as well as their degradation products. MS decomposition is used for the determinations of these compounds, when the so-called multiple-reaction monitoring is applied during liquid chromatography (LC)/ESI-MS analysis. Thus, better understanding of MS decompositions of the above compounds seems to be important.

A critical review of the novelties in the development of intravenous nanoemulsions.

Nanoemulsions have gained increasing attention in recent years as a drug delivery system due to their ability to improve the solubility and bioavailability of poorly water-soluble drugs. This systematic review aimed to collect and critically analyze recent novelties in developing, designing, and optimizing intravenous nanoemulsions appearing in articles published between 2017 and 2022. The applied methodology involved searching two electronic databases PubMed and Scopus, using the keyword "nanoemulsion" in combination with "intravenous" or "parenteral". The resulting original articles were classified by the method of preparation into different categories. An overview of the current methods used for the preparation of such formulations, including high- and low-energy emulsification, was provided. The advantages and disadvantages of these methods were discussed, as well as their potential impact on the properties of the developed intravenous nanoemulsions. The problem of inconsistency in intravenous nanoemulsion terminology may lead to misunderstandings and misinterpretations of their properties and applications was also undertaken. Finally, the regulatory aspects of intravenous nanoemulsions, the state of the art in the field of intravenous emulsifiers, and the future perspectives were presented.

The Development of Magnolol-Loaded Intravenous Emulsion with Low Hepatotoxic Potential.

Intestinal failure-associated liver disease (IFALD) is a severe liver injury occurring due to factors related to intestinal failure and parenteral nutrition administration. Different approaches are studied to reduce the risk or ameliorate the course of IFALD, including providing omega-3 fatty acids instead of soybean oil-based lipid emulsion or administering active compounds that exert a hepatoprotective effect. This study aimed to develop, optimize, and characterize magnolol-loaded intravenous lipid emulsion for parenteral nutrition. The preformulation studies allowed for chosen oils mixture of the highest capacity of magnolol solubilization. Then, magnolol-loaded SMOFlipid was developed using the passive incorporation method. The Box-Behnken design and response surface methodology were used to optimize the entrapment efficiency. The optimal formulation was subjected to short-term stress tests, and its effect on normal human liver cells and erythrocytes was determined using the MTT and hemolysis tests, respectively. The optimized magnolol-loaded SMOFlipid was characterized by the mean droplet diameter of 327.6 ± 2.9 nm with a polydispersity index of 0.12 ± 0.02 and zeta potential of -32.8 ± 1.2 mV. The entrapment efficiency of magnolol was above 98%, and pH and osmolality were sufficient for intravenous administration. The magnolol-loaded SMOFlipid samples showed a significantly lower toxic effect than bare SMOFlipid in the same concentration on THLE-2 cells, and revealed an acceptable hemolytic effect of 8.3%. The developed formulation was characterized by satisfactory stability. The in vitro studies showed the reduced cytotoxic effect of MAG-SMOF applied in high concentrations compared to bare SMOFlipid and the non-hemolytic effect on human blood cells. The magnolol-loaded SMOFlipid is promising for further development of hepatoprotective lipid emulsion for parenteral nutrition.

Honokiol-Loaded Nanoemulsion for Glioblastoma Treatment: Statistical Optimization, Physicochemical Characterization, and an In Vitro Toxicity Assay.

BACKGROUND: Glioblastoma (GBM) is an extremely invasive and heterogenous malignant brain tumor. Despite advances in current anticancer therapy, treatment options for glioblastoma remain limited, and tumor recurrence is inevitable. Therefore, alternative therapies or new active compounds that can be used as adjuvant therapy are needed. This study aimed to develop, optimize, and characterize honokiol-loaded nanoemulsions intended for intravenous administration in glioblastoma therapy. METHODS: Honokiol-loaded nanoemulsion was developed by incorporating honokiol into Lipofundin MCT/LCT 20% using a horizontal shaker. The Box-Behnken design, coupled with response surface methodology, was used to optimize the incorporation process. The effect of the developed formulation on glioblastoma cell viability was determined using the MTT test. Long-term and short-term stress tests were performed to evaluate the effect of honokiol on the stability of the oil-in-water system and the effect of different stress factors on the stability of honokiol, respectively. Its physicochemical properties, such as MDD, PDI, ZP, OSM, pH, and loading efficiency (LE%), were determined. RESULTS: The optimized honokiol-loaded nanoemulsion was characterized by an MDD of 201.4 (0.7) nm with a PDI of 0.07 (0.02) and a ZP of -28.5 (0.9) mV. The LE% of honokiol was above 95%, and pH and OSM were sufficient for intravenous administration. The developed formulation was characterized by good stability and a satisfactory toxicity effect of the glioblastoma cell lines. CONCLUSIONS: The honokiol-loaded nanoemulsion is a promising pharmaceutical formulation for further development in the adjuvant therapy of glioblastoma.