Untargeted search and identification of metabolites of antiviral agent camphecene in rat urine by liquid chromatography and mass spectrometry and studying their distribution in organs following peroral administration of the compound

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Untargeted search and identification of metabolites of antiviral agent camphecene in rat urine by liquid chromatography and mass spectrometry and studying their distribution in organs following peroral administration of the compound. / Rogachev, Artem D.; Yarovaya, Olga I.; Fatianova, Alina V. et al.

In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 161, 30.11.2018, p. 383-392.

Research output: Contribution to journal › Article › peer-review

BibTeX

@article{4351f6de135c46acb2b95fdf5ba50d4a,

title = "Untargeted search and identification of metabolites of antiviral agent camphecene in rat urine by liquid chromatography and mass spectrometry and studying their distribution in organs following peroral administration of the compound",

abstract = "Major metabolites of camphecene, a new effective antiviral agent, formed after its oral administration to rats and excreted in the urine, were found and identified using liquid chromatography coupled to mass spectrometry as well as multivariate analysis of HPLC-MS data. The metabolites were found to be camphecene glucuronide, camphecene sulfate and the corresponding iminoacid. A study of the dynamics of accumulation of camphecene and its metabolites in the liver, kidneys, lungs and brain of animals was performed. Maximum concentration of camphecene in blood and organs was reached after 1.5–2 h of its administration, and the maximal content of the agent in the organs investigated was observed in the kidneys. The content of the substance in the lungs was comparable to that in the liver. Also, camphecene was found in brain in high concentration, thus allowing assumption of its ability to penetrate the blood-brain barrier and to exert its antiviral properties in the organ. Camphecene glucuronide and iminoacid had concentration-time profiles similar to that of their precursor, their content being maximal in kidney and liver and 2–3 orders of magnitude higher than in lungs and brain. The content of camphecene sulfate was of similar level in all organs studied. The results obtained made it possible to develop recommendations for therapy with the use of camphecene.",

keywords = "Antiviral drugs, Camphecene, Liquid chromatography, Metabolites, Pharmacokinetics, Tandem mass spectrometry, IN-VITRO, METABOLOMICS, QUANTIFICATION, VALIDATION, INFLUENZA-VIRUS, Multivariate Analysis, Camphor/administration & dosage, Administration, Oral, Rats, Ethanolamines/administration & dosage, Tissue Distribution, Tandem Mass Spectrometry, Animals, Chromatography, Liquid, Antiviral Agents/administration & dosage",

author = "Rogachev, {Artem D.} and Yarovaya, {Olga I.} and Fatianova, {Alina V.} and Lavrinenko, {Valentina A.} and Amosov, {Evgeny V.} and Zarubaev, {Vladimir V.} and Pokrovsky, {Andrey G.} and Salakhutdinov, {Nariman F.}",

note = "Publisher Copyright: {\textcopyright} 2018 Elsevier B.V.",

year = "2018",

month = nov,

day = "30",

doi = "10.1016/j.jpba.2018.09.003",

language = "English",

volume = "161",

pages = "383--392",

journal = "Journal of Pharmaceutical and Biomedical Analysis",

issn = "0731-7085",

publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Untargeted search and identification of metabolites of antiviral agent camphecene in rat urine by liquid chromatography and mass spectrometry and studying their distribution in organs following peroral administration of the compound

AU - Rogachev, Artem D.

AU - Yarovaya, Olga I.

AU - Fatianova, Alina V.

AU - Lavrinenko, Valentina A.

AU - Amosov, Evgeny V.

AU - Zarubaev, Vladimir V.

AU - Pokrovsky, Andrey G.

AU - Salakhutdinov, Nariman F.

PY - 2018/11/30

Y1 - 2018/11/30

N2 - Major metabolites of camphecene, a new effective antiviral agent, formed after its oral administration to rats and excreted in the urine, were found and identified using liquid chromatography coupled to mass spectrometry as well as multivariate analysis of HPLC-MS data. The metabolites were found to be camphecene glucuronide, camphecene sulfate and the corresponding iminoacid. A study of the dynamics of accumulation of camphecene and its metabolites in the liver, kidneys, lungs and brain of animals was performed. Maximum concentration of camphecene in blood and organs was reached after 1.5–2 h of its administration, and the maximal content of the agent in the organs investigated was observed in the kidneys. The content of the substance in the lungs was comparable to that in the liver. Also, camphecene was found in brain in high concentration, thus allowing assumption of its ability to penetrate the blood-brain barrier and to exert its antiviral properties in the organ. Camphecene glucuronide and iminoacid had concentration-time profiles similar to that of their precursor, their content being maximal in kidney and liver and 2–3 orders of magnitude higher than in lungs and brain. The content of camphecene sulfate was of similar level in all organs studied. The results obtained made it possible to develop recommendations for therapy with the use of camphecene.

AB - Major metabolites of camphecene, a new effective antiviral agent, formed after its oral administration to rats and excreted in the urine, were found and identified using liquid chromatography coupled to mass spectrometry as well as multivariate analysis of HPLC-MS data. The metabolites were found to be camphecene glucuronide, camphecene sulfate and the corresponding iminoacid. A study of the dynamics of accumulation of camphecene and its metabolites in the liver, kidneys, lungs and brain of animals was performed. Maximum concentration of camphecene in blood and organs was reached after 1.5–2 h of its administration, and the maximal content of the agent in the organs investigated was observed in the kidneys. The content of the substance in the lungs was comparable to that in the liver. Also, camphecene was found in brain in high concentration, thus allowing assumption of its ability to penetrate the blood-brain barrier and to exert its antiviral properties in the organ. Camphecene glucuronide and iminoacid had concentration-time profiles similar to that of their precursor, their content being maximal in kidney and liver and 2–3 orders of magnitude higher than in lungs and brain. The content of camphecene sulfate was of similar level in all organs studied. The results obtained made it possible to develop recommendations for therapy with the use of camphecene.

KW - Antiviral drugs

KW - Camphecene

KW - Liquid chromatography

KW - Metabolites

KW - Pharmacokinetics

KW - Tandem mass spectrometry

KW - IN-VITRO

KW - METABOLOMICS

KW - QUANTIFICATION

KW - VALIDATION

KW - INFLUENZA-VIRUS

KW - Multivariate Analysis

KW - Camphor/administration & dosage

KW - Administration, Oral

KW - Rats

KW - Ethanolamines/administration & dosage

KW - Tissue Distribution

KW - Tandem Mass Spectrometry

KW - Animals

KW - Chromatography, Liquid

KW - Antiviral Agents/administration & dosage

UR - http://www.scopus.com/inward/record.url?scp=85053053976&partnerID=8YFLogxK

U2 - 10.1016/j.jpba.2018.09.003

DO - 10.1016/j.jpba.2018.09.003

M3 - Article

C2 - 30205302

AN - SCOPUS:85053053976

VL - 161

SP - 383

EP - 392

JO - Journal of Pharmaceutical and Biomedical Analysis

JF - Journal of Pharmaceutical and Biomedical Analysis

SN - 0731-7085

ER -

ID: 16481735