Tissue distribution of OL9-116, a Tdp1 inhibitor based on usnic acid, is significantly altered in Lewis lung carcinoma-bearing mice compared to healthy animals

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Tissue distribution of OL9-116, a Tdp1 inhibitor based on usnic acid, is significantly altered in Lewis lung carcinoma-bearing mice compared to healthy animals. / Okhina, Alina A.; Kornienko, Tatyana E.; Rogachev, Artem D. et al.

In: Journal of Pharmaceutical and Biomedical Analysis, Vol. 265, 117054, 15.11.2025.

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

BibTeX

@article{bc4d24f3bea84cf5847acfbc98e537d1,

title = "Tissue distribution of OL9-116, a Tdp1 inhibitor based on usnic acid, is significantly altered in Lewis lung carcinoma-bearing mice compared to healthy animals",

abstract = "In the present study, we developed and validated three liquid chromatography–tandem mass spectrometry (LC–MS/MS) methods for quantification of the agent OL9–116, a Tdp1 inhibitor based on usnic acid, in murine lungs, liver and kidney, respectively. Additionally, a semi-quantitative method was developed for quantification of the agent in the primary tumor node of Lewis lung carcinoma. Tissue samples were prepared using ultrasonic homogenization and QuEChERS methodology. The quantification of the compound was performed using SCIEX 6500 QTRAP mass spectrometer in MRM mode following a chromatographic separation on a C8 reversed-phase column. The methods were validated in terms of selectivity, calibration curve, accuracy, precision, recovery, matrix factor and stability of the prepared sample, and subsequently applied for quantification of the agent OL9–116 in the organs of healthy and tumor-bearing mice following a single intragastric administration of the substance at a dose of 150 mg/kg. A comparison of the distribution of OL9–116 in the organs of the animals demonstrated that the presence of the tumor significantly altered the pharmacokinetics of the substance, reducing its bioavailability, which should be taken into account when developing tumor treatment strategies.",

keywords = "LC[sbnd]MS/MS, QuEChERS methodology, Tdp1 inhibitor, Tissue homogenate, Usnic acid",

author = "Okhina, {Alina A.} and Kornienko, {Tatyana E.} and Rogachev, {Artem D.} and Luzina, {Olga A.} and Popova, {Nelly A.} and Nikolin, {Valery P.} and Zakharenko, {Alexandra L.} and Dyrkheeva, {Nadezhda S.} and Pokrovsky, {Andrey G.} and Salakhutdinov, {Nariman F.} and Lavrik, {Olga I.}",

note = "Synthesis of the investigated agent was carried out within the framework of the state assignment No. 075–00365–25–00 (Novosibirsk Institute of Organic Chemistry SB RAS); experiments on animals were supported by state assignments No. 125012300658–9 (Institute of Chemical Biology and Fundamental Medicine SB RAS) and No. FWNR-2022–0016 (Institute of Cytology and Genetics SB RAS); LC–MS/MS analyses were supported by the state assignment FSUS-2025–0012 (Novosibirsk State University).",

year = "2025",

month = nov,

day = "15",

doi = "10.1016/j.jpba.2025.117054",

language = "English",

volume = "265",

journal = "Journal of Pharmaceutical and Biomedical Analysis",

issn = "0731-7085",

publisher = "Elsevier Science Publishing Company, Inc.",

}

RIS

TY - JOUR

T1 - Tissue distribution of OL9-116, a Tdp1 inhibitor based on usnic acid, is significantly altered in Lewis lung carcinoma-bearing mice compared to healthy animals

AU - Okhina, Alina A.

AU - Kornienko, Tatyana E.

AU - Rogachev, Artem D.

AU - Luzina, Olga A.

AU - Popova, Nelly A.

AU - Nikolin, Valery P.

AU - Zakharenko, Alexandra L.

AU - Dyrkheeva, Nadezhda S.

AU - Pokrovsky, Andrey G.

AU - Salakhutdinov, Nariman F.

AU - Lavrik, Olga I.

N1 - Synthesis of the investigated agent was carried out within the framework of the state assignment No. 075–00365–25–00 (Novosibirsk Institute of Organic Chemistry SB RAS); experiments on animals were supported by state assignments No. 125012300658–9 (Institute of Chemical Biology and Fundamental Medicine SB RAS) and No. FWNR-2022–0016 (Institute of Cytology and Genetics SB RAS); LC–MS/MS analyses were supported by the state assignment FSUS-2025–0012 (Novosibirsk State University).

PY - 2025/11/15

Y1 - 2025/11/15

N2 - In the present study, we developed and validated three liquid chromatography–tandem mass spectrometry (LC–MS/MS) methods for quantification of the agent OL9–116, a Tdp1 inhibitor based on usnic acid, in murine lungs, liver and kidney, respectively. Additionally, a semi-quantitative method was developed for quantification of the agent in the primary tumor node of Lewis lung carcinoma. Tissue samples were prepared using ultrasonic homogenization and QuEChERS methodology. The quantification of the compound was performed using SCIEX 6500 QTRAP mass spectrometer in MRM mode following a chromatographic separation on a C8 reversed-phase column. The methods were validated in terms of selectivity, calibration curve, accuracy, precision, recovery, matrix factor and stability of the prepared sample, and subsequently applied for quantification of the agent OL9–116 in the organs of healthy and tumor-bearing mice following a single intragastric administration of the substance at a dose of 150 mg/kg. A comparison of the distribution of OL9–116 in the organs of the animals demonstrated that the presence of the tumor significantly altered the pharmacokinetics of the substance, reducing its bioavailability, which should be taken into account when developing tumor treatment strategies.

AB - In the present study, we developed and validated three liquid chromatography–tandem mass spectrometry (LC–MS/MS) methods for quantification of the agent OL9–116, a Tdp1 inhibitor based on usnic acid, in murine lungs, liver and kidney, respectively. Additionally, a semi-quantitative method was developed for quantification of the agent in the primary tumor node of Lewis lung carcinoma. Tissue samples were prepared using ultrasonic homogenization and QuEChERS methodology. The quantification of the compound was performed using SCIEX 6500 QTRAP mass spectrometer in MRM mode following a chromatographic separation on a C8 reversed-phase column. The methods were validated in terms of selectivity, calibration curve, accuracy, precision, recovery, matrix factor and stability of the prepared sample, and subsequently applied for quantification of the agent OL9–116 in the organs of healthy and tumor-bearing mice following a single intragastric administration of the substance at a dose of 150 mg/kg. A comparison of the distribution of OL9–116 in the organs of the animals demonstrated that the presence of the tumor significantly altered the pharmacokinetics of the substance, reducing its bioavailability, which should be taken into account when developing tumor treatment strategies.

KW - LC[sbnd]MS/MS

KW - QuEChERS methodology

KW - Tdp1 inhibitor

KW - Tissue homogenate

KW - Usnic acid

UR - https://www.mendeley.com/catalogue/241fc080-c65e-3b1b-aa53-10d69917843a/

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=105010612936&origin=inward

U2 - 10.1016/j.jpba.2025.117054

DO - 10.1016/j.jpba.2025.117054

M3 - Article

C2 - 40669139

VL - 265

JO - Journal of Pharmaceutical and Biomedical Analysis

JF - Journal of Pharmaceutical and Biomedical Analysis

SN - 0731-7085

M1 - 117054

ER -

ID: 68546146