Development of a method for the quantitative determination of the solubility limits of poorly soluble in water substances on the example of quercetin

Nataliia Khanina; Victoriya Georgiyants; Vadim Khanin

doi:10.15587/2519-4852.2023.283293

Authors

Nataliia Khanina National University of Pharmacy; Meitheal Pharmaceuticals (USA), Ukraine https://orcid.org/0000-0002-8400-2163
Victoriya Georgiyants National University of Pharmacy, Ukraine http://orcid.org/0000-0001-8794-8010
Vadim Khanin National University of Pharmacy, Ukraine https://orcid.org/0000-0001-7588-5526

DOI:

https://doi.org/10.15587/2519-4852.2023.283293

Keywords:

quercetin, identification, quantitative definition, HPLC, method development, bioequivalence, biowaiver, mass spectrometry, solubility, dissolution testing

Abstract

Aim. To consider the importance of this physicochemical characteristic as a determining factor in the study of bioequivalence and bioavailability, there is a need to develop a method to quantitatively determine the solubility limit of quercetin.

Materials and methods. The quercetin concentration was determined in the obtained samples using chromatographic and external standard methods. The pharmacopeial standard – PS of the SPU was used as a standard. For measurements, an Agilent 1290 liquid chromatograph with an Agilent 6530 TOF mass spectrometric detector was used, using a 50×4.6 mm column filled with a sorbent with a grafted phase of octyl silica gel, particle size – 1.7 μm.

Results. The exact limit of the solubility of quercetin, as a poorly soluble substance, has been established. Based on the data obtained, the kinetics of the dissolution of quercetin was studied. In tandem with the QTOF mass spectrometric detector, the HPLC method was utilized in the identification and quantification process. To accurately determine the point that will correspond to the solubility limit of quercetin in water, the obtained experimental dependence was approximated by a polynomial dependence, for which, by solving a system of equations in the Microsoft Excel program, concentration values were found corresponding to the inflection points of the studied dependences.

Conclusions. When studying their bioavailability, a new approach has been developed to quantitatively determine the solubility limit of difficult or practically insoluble substances in aqueous media with a neutral pH value. The exact value of the solubility limit for the test sample of quercetin was established, which was 3.02 mcg/ml. The kinetics of the release of quercetin in aqueous solutions was studied

Author Biographies

Nataliia Khanina, National University of Pharmacy; Meitheal Pharmaceuticals (USA)

PhD Student

Department of Pharmaceutical Chemistry;

Senior Associate manager of Regulatory Affairs

Victoriya Georgiyants, National University of Pharmacy

Doctor of Pharmaceutical Sciences, Professor, Head of Department

Department of Pharmaceutical Chemistry

Vadim Khanin, National University of Pharmacy

PhD Chemistry, QC Specialist

State Laboratory of Drug Quality Control

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