Publication: HPLC ANALYSIS OF EVEROLIMUS INTERACTING WITH NATURAL COMPOUNDS RUTIN, QUERCETIN AND CURCUMIN IN DIFFERENT pH ENVIRONMENTS.
Date
2024
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
IMU University
Abstract
Everolimus is a mammalian target of a rapamycin inhibitor drug approved for treating advanced-stage, metastatic cancer that is non-responsive to endocrine therapy. Like most chemotherapeutic drugs, everolimus comes with numerous side effects, and the severity of these side effects often varies from patient to patient. In hopes of curbing the side effects during the treatment process, it was reported that some patients default to complementary and alternative medicine (CAM) in the form of natural product-based dietary supplements. One of the natural product supplements that was reported to have been consumed by patients undergoing everolimus treatment is curcumin. Following the consumption of curcumin during everolimus treatment is a significant fall in everolimus blood concentration levels (Cmin.). It was speculated that curcumin induces CYP3A4 activity, thus increasing everolimus metabolism. However, whether the effects of curcumin on everolimus metabolism are CYP3A4-related is yet to be proven, as there are other possible ways for curcumin to be involved in decreasing everolimus Cmin in patients. One of them includes the possibility of physicochemical interaction.
The primary objective of this project was to investigate the potential chemical interaction(s) that could occur between everolimus and certain selected natural compounds (rutin, quercetin and curcumin) when present in an aqueous matrix under different physiological pH environments via HPLC. The occurrences of said interactions are depicted by the appearance of unknown peaks in sample chromatograms whereby everolimus was paired with other foreign compounds. These unknown peaks were not detected in the control samples, whereby everolimus stands as the lone compound. Not all peaks present in the sample chromatograms are integrated and quantified. As a pre-requisite, the unknown peaks that are isolated in sample chromatograms mustn’t be present in blanks or controls. Only the unknown peaks that share the same spectral profile as the primary molecule, everolimus are captured and quantified. Based on the findings of this investigation, everolimus is most unstable in the presence of the natural compounds when incubated in pH 6.8 medium. The degree of instability of everolimus was depicted by the number of unknown peaks present. This indicates that more chemical interactions take place between everolimus and the natural compounds at a pH 6.8 environment compared to other pHs. Also, in pH 6.8, everolimus is most unstable and degrades rapidly when paired individually with the natural compound quercetin. The extent of interaction that takes place between everolimus and each natural compound differs. When in the presence of all three natural compounds at once, the rate of degradation of everolimus is highest at pH 6.8. The rate of degradation is interpreted as the formation of unknown peaks per unit time. However, in a pH 4.5 environment, everolimus has the most interaction when individually paired with curcumin. Most of the unknown peaks observed in single-paired samples are not found in the control sample. Based on the evidence gathered, the stability of everolimus in different pH environments is highly affected by the presence of natural compounds.
Description
Keywords
Everolimus, Sirolimus, Anti-Bacterial Agents, Dietary Supplements, Biological Products, Curcumin, Chromatography, High Pressure Liquid