APPROACHES TO THE DEVELOPMENT OF BIOANALYTICAL METHODS FOR DETERMINATION OF UNSTABLE SUBSTANCES IN BIOLOGICAL FLUIDS

The approaches to bioanalytical method development for determination of substances which contain unstable functional groups in the structure are described. The oxidation and the hydrolysis are main causes of the decomposition of substances in biological fluids. Phenolic hydroxyls contain drugs were...

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Autores principales:	A. L. Khokhlov, I. I. Yaichkov, Yu. A. Dzhurko, M. Ryska, V. Kubeš, L. N. Shitov
Formato:	article
Lenguaje:	RU
Publicado:	Scientific Сentre for Family Health and Human Reproduction Problems 2018
Materias:	instability back conversion plasma mycophenolic acid methyldopa desmethyl mebeverine acid Science Q
Acceso en línea:	https://doaj.org/article/9dd78bef457d4735a876f2f5642c7051
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spelling	oai:doaj.org-article:9dd78bef457d4735a876f2f5642c70512021-11-23T06:14:41ZAPPROACHES TO THE DEVELOPMENT OF BIOANALYTICAL METHODS FOR DETERMINATION OF UNSTABLE SUBSTANCES IN BIOLOGICAL FLUIDS2541-94202587-959610.29413/ABS.2018-3.5.16https://doaj.org/article/9dd78bef457d4735a876f2f5642c70512018-09-01T00:00:00Zhttps://www.actabiomedica.ru/jour/article/view/715https://doaj.org/toc/2541-9420https://doaj.org/toc/2587-9596The approaches to bioanalytical method development for determination of substances which contain unstable functional groups in the structure are described. The oxidation and the hydrolysis are main causes of the decomposition of substances in biological fluids. Phenolic hydroxyls contain drugs were selected as examples of oxidable compounds, glucuronides of drugs were selected as examples of hydrolysable compounds. Determination of mycophenolic acid, which contains one phenolic hydroxyl and metabolized by formation of glucuronides, in plasma was performed using high performance liquid chromatography with mass-spectrometry and tandem mass-spectrometry detection. Methyldopa, which contains two phenolic hydroxyls, in stabilized plasma was assayed by high performance liquid chromatography – tandem mass-spectrometry in the range of 0.02–3.00 μg/ml. Concentrations of desmethyl mebeverine acid, which contains in the structure one phenolic hydroxyl and metabolized by formation of phenolic glucuronide, was measured simultaneously with mebeverine acid in the range of 10–2000 ng/ml. The influence of the ion source conversion of glucuronides on the quantitative determination of the substances was studied in the initial part of methods development. The next, selection of anticoagulants based on the study of short-term stability and freeze/thaw stability of the analytes and back conversion of their glucuronides was performed. The combination of anticoagulant K3EDTA and the antioxidant solution containing a mixture of ascorbic acid, sodium sulfite and sodium hydrogen carbonate in the concentrations of 5.0 %, 0.2 % and 2.4 %, respectively, was used to prevent degradation of methyldopa.A. L. KhokhlovI. I. YaichkovYu. A. DzhurkoM. RyskaV. KubešL. N. ShitovScientific Сentre for Family Health and Human Reproduction Problemsarticleinstabilityback conversionplasmamycophenolic acidmethyldopadesmethyl mebeverine acidScienceQRUActa Biomedica Scientifica, Vol 3, Iss 5, Pp 106-115 (2018)
institution	DOAJ
collection	DOAJ
language	RU
topic	instability back conversion plasma mycophenolic acid methyldopa desmethyl mebeverine acid Science Q
spellingShingle	instability back conversion plasma mycophenolic acid methyldopa desmethyl mebeverine acid Science Q A. L. Khokhlov I. I. Yaichkov Yu. A. Dzhurko M. Ryska V. Kubeš L. N. Shitov APPROACHES TO THE DEVELOPMENT OF BIOANALYTICAL METHODS FOR DETERMINATION OF UNSTABLE SUBSTANCES IN BIOLOGICAL FLUIDS
description	The approaches to bioanalytical method development for determination of substances which contain unstable functional groups in the structure are described. The oxidation and the hydrolysis are main causes of the decomposition of substances in biological fluids. Phenolic hydroxyls contain drugs were selected as examples of oxidable compounds, glucuronides of drugs were selected as examples of hydrolysable compounds. Determination of mycophenolic acid, which contains one phenolic hydroxyl and metabolized by formation of glucuronides, in plasma was performed using high performance liquid chromatography with mass-spectrometry and tandem mass-spectrometry detection. Methyldopa, which contains two phenolic hydroxyls, in stabilized plasma was assayed by high performance liquid chromatography – tandem mass-spectrometry in the range of 0.02–3.00 μg/ml. Concentrations of desmethyl mebeverine acid, which contains in the structure one phenolic hydroxyl and metabolized by formation of phenolic glucuronide, was measured simultaneously with mebeverine acid in the range of 10–2000 ng/ml. The influence of the ion source conversion of glucuronides on the quantitative determination of the substances was studied in the initial part of methods development. The next, selection of anticoagulants based on the study of short-term stability and freeze/thaw stability of the analytes and back conversion of their glucuronides was performed. The combination of anticoagulant K3EDTA and the antioxidant solution containing a mixture of ascorbic acid, sodium sulfite and sodium hydrogen carbonate in the concentrations of 5.0 %, 0.2 % and 2.4 %, respectively, was used to prevent degradation of methyldopa.
format	article
author	A. L. Khokhlov I. I. Yaichkov Yu. A. Dzhurko M. Ryska V. Kubeš L. N. Shitov
author_facet	A. L. Khokhlov I. I. Yaichkov Yu. A. Dzhurko M. Ryska V. Kubeš L. N. Shitov
author_sort	A. L. Khokhlov
title	APPROACHES TO THE DEVELOPMENT OF BIOANALYTICAL METHODS FOR DETERMINATION OF UNSTABLE SUBSTANCES IN BIOLOGICAL FLUIDS
title_short	APPROACHES TO THE DEVELOPMENT OF BIOANALYTICAL METHODS FOR DETERMINATION OF UNSTABLE SUBSTANCES IN BIOLOGICAL FLUIDS
title_full	APPROACHES TO THE DEVELOPMENT OF BIOANALYTICAL METHODS FOR DETERMINATION OF UNSTABLE SUBSTANCES IN BIOLOGICAL FLUIDS
title_fullStr	APPROACHES TO THE DEVELOPMENT OF BIOANALYTICAL METHODS FOR DETERMINATION OF UNSTABLE SUBSTANCES IN BIOLOGICAL FLUIDS
title_full_unstemmed	APPROACHES TO THE DEVELOPMENT OF BIOANALYTICAL METHODS FOR DETERMINATION OF UNSTABLE SUBSTANCES IN BIOLOGICAL FLUIDS
title_sort	approaches to the development of bioanalytical methods for determination of unstable substances in biological fluids
publisher	Scientific Сentre for Family Health and Human Reproduction Problems
publishDate	2018
url	https://doaj.org/article/9dd78bef457d4735a876f2f5642c7051
work_keys_str_mv	AT alkhokhlov approachestothedevelopmentofbioanalyticalmethodsfordeterminationofunstablesubstancesinbiologicalfluids AT iiyaichkov approachestothedevelopmentofbioanalyticalmethodsfordeterminationofunstablesubstancesinbiologicalfluids AT yuadzhurko approachestothedevelopmentofbioanalyticalmethodsfordeterminationofunstablesubstancesinbiologicalfluids AT mryska approachestothedevelopmentofbioanalyticalmethodsfordeterminationofunstablesubstancesinbiologicalfluids AT vkubes approachestothedevelopmentofbioanalyticalmethodsfordeterminationofunstablesubstancesinbiologicalfluids AT lnshitov approachestothedevelopmentofbioanalyticalmethodsfordeterminationofunstablesubstancesinbiologicalfluids
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APPROACHES TO THE DEVELOPMENT OF BIOANALYTICAL METHODS FOR DETERMINATION OF UNSTABLE SUBSTANCES IN BIOLOGICAL FLUIDS

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