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DEVELOPMENT AND VALIDATION OF HPLC-MS/MS METHOD FOR MOLSIDOMINE QUANTITATION IN VARIOUS TISSUES OF RATS

DOI: https://doi.org/10.29296/25877313-2023-04-06
Issue: 
4
Year: 
2023

N.S. Popov
Ph.D. (Pharm.), Head of Research Laboratory, Associate Professor, Department of Pharmacology and Clinical Pharmacology,
Tver State Medical University (Tver, Russia)
ORCID: 0000-0002-1792-7414
E-mail: ns.popov@mail.ru
V.Yu. Balabanyan
Dr.Sc. (Pharm.), Associate Professor, Leading Research Scientist, Laboratory of Translational Medicine,
Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University (Moscow, Russia)
ORCID: 0000-0002-5744-7060
M.S. Baranov
Ph.D. (Chem.),
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences (Moscow, Russia)
ORCID: 0000-0002-9339-7603

Relevance. Molsidomine is a vasoactive drug from the group of sydnonymines widely used in clinical practice. The use of molsidomine as a compar-ison drug during pharmacokinetic studies of new pharmacological agents of the sidnonymine group requires the development and implementation of accurate and reproducible methods for the quantitative determination of this drug in the organs and tissues of experimental animals. Purpose of the study. Development and validation of a method for quantitative determination of molsidomine in various rat tissues using HPLC-MS/MS. Materials and methods. Quantitative determination of molsidomine in blood plasma and homogenates of rat tissues was carried out by high-performance liquid chromatography with mass spectrometric detection. Method of precipitation of proteins with methanol was applied as a sample preparation of biological material. An Agilent Infinity LabPoroshell 120 EC-C18 4.6x100 mm 2.7 Micron column was used for chromatographic separation using an aqueous solution of methanol. Results. The developed bioanalytical method was validated according to the following parameters: selectivity, matrix effect, sample transfer, linearity of the analytical range, lower limit of quantitative determination (NPCO), intra- and inter-series accuracy and precision, dilution factor, stability of the studied substances at the stages of analysis. Conclusion. A method of quantitative determination of molsidomine in blood plasma and homogenates of rat tissues has been developed and vali-dated. The analytical range for blood plasma, liver, kidney, brain and spleen homogenates was 5.0–1000.0 ng/ml; for skeletal muscle and heart tissue homogenates was 1.0-1000.0 ng/ml; for adipose tissue homogenate was 10.0–1000.0 ng/ml. This study allows us to use the developed methodology for conducting the analytical part of pharmacokinetic studies of molsidomine.
Keywords: 
molsidomine
HPLC-MS/MS
validation
pharmacokinetics
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