DETERMINATION OF 3-HYDROXY-3-PYRROLINE-2-ONE IN URINE AND STUDY OF ITS EXCRETION FROM THE ORGANISM OF LABORATORY ANIMALS


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Abstract

It is known that almost any disease of the central nervous system is accompanied by the development of cognitive disorders. The drugs of choice in the complex therapy in this case are nootropics. On the world market racetam group, i.e. derivatives of alpha-pyrrolidone, prevails among nootropics, and the derivatives have a wide spectrum of pharmacological activity. Currently, this group continues to expand. By the employees of Perm State Pharmaceutical Academy (PSPA), ruled by Professor V.L. Gein, a new biologically active compound, a 3-pyrrolin-2-one derivative KOH-1 was synthesized. This compound is at the preclinical research stage now.The aim of this work was the development of methods for determination of KOH-1 in urine by high performance liquid chromatography (HPLC), the study of excretion KOH-1 from the organism of laboratory animals.Materials and methods. Studies on the development of methods were carried out by using a liquid chromatograph LC-20 Prominence (Shimadzu, Japan) with a diode-array detector. The validation was carried out in accordance with the requirements for bioanalytical methods, in terms of selectivity, linearity, precision and accuracy. The study of excretion of KOH-1 was performed on white non-linear male rats weighing 300-400 g. The substance KOH-1 was administered once orally in a suspension of starch mucus at a dose of 100 mg/kg.Results and discussion. As a result of the research, the  method for determining the biologically active compound KOH-1 in urine has been developed. The validation showed its suitability for pharmacokinetic studies. The data on daily excretion of KOH-1 in urine after a single oral administration to rats were obtained.Conclusion. The developed conditions for the chromatographic determination of KOH-1 in urine can be used in pharmacokinetic studies, both at the preclinical and clinical stages of the study of a potential drug. The data on excretion of KOH-1 will allow to determine the ways of excretion of the preparation, and also to select a rational dosage, to identify possible contraindications to the use.

About the authors

E. A. Bulgakova

Perm State Pharmaceutical Academy

Email: karpenko_pfa@mail.ru

Yu. N. Karpenko

Perm State Pharmaceutical Academy

Email: fake@neicon.ru

T. I. Yarygina

Perm State Pharmaceutical Academy

Email: bugakova_pfa@mail.ru

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Copyright (c) 2017 Bulgakova E.A., Karpenko Y.N., Yarygina T.I.

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