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Article

High-Throughput Method for the Simultaneous Determination of Doxorubicin Metabolites in Rat Urine after Treatment with Different Drug Nanoformulations

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Faculty of Pharmacy and Biochemistry, University of Zagreb, Ante Kovačića 1, 10000 Zagreb, Croatia
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Poliklinika Prof. Nikša Drinković, Boškovićeva Ul. 15, 10000 Zagreb, Croatia
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Institute for Medical Research and Occupational Health, Ksaverska Cesta 2, 10000 Zagreb, Croatia
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Rudjer Boskovic Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia
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MyBiotech GmbH, Industriestraße 1B, 66802 Überherrn, Germany
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Centre for Research and Knowledge Transfer in Biotechnology, University of Zagreb, Rockefellerova 10, 10000 Zagreb, Croatia
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Authors to whom correspondence should be addressed.
Academic Editors: Jérôme Guitton and Hiroyuki Kataoka
Molecules 2022, 27(4), 1177; https://doi.org/10.3390/molecules27041177
Received: 13 December 2021 / Revised: 28 January 2022 / Accepted: 6 February 2022 / Published: 9 February 2022
(This article belongs to the Special Issue Advanced Analytical Technologies for Anti-cancer Drugs Analysis)
Doxorubicin (DOX) is one of the most effective cytotoxic agents against malignant diseases. However, the clinical application of DOX is limited, due to dose-related toxicity. The development of DOX nanoformulations that significantly reduce its toxicity and affect the metabolic pathway of the drug requires improved methods for the quantitative determination of DOX metabolites with high specificity and sensitivity. This study aimed to develop a high-throughput method based on high-performance liquid chromatography with fluorescence detection (HPLC-FD) for the quantification of DOX and its metabolites in the urine of laboratory animals after treatment with different DOX nanoformulations. The developed method was validated by examining its specificity and selectivity, linearity, accuracy, precision, limit of detection, and limit of quantification. The DOX and its metabolites, doxorubicinol (DOXol) and doxorubicinone (DOXon), were successfully separated and quantified using idarubicin (IDA) as an internal standard (IS). The linearity was obtained over a concentration range of 0.05–1.6 μg/mL. The lowest limit of detection and limit of quantitation were obtained for DOXon at 5.0 ng/mL and 15.0 ng/mL, respectively. For each level of quality control (QC) samples, the inter- and intra-assay precision was less than 5%. The accuracy was in the range of 95.08–104.69%, indicating acceptable accuracy and precision of the developed method. The method was applied to the quantitative determination of DOX and its metabolites in the urine of rats treated by novel nanoformulated poly(lactic-co-glycolic acid) (DOX-PLGA), and compared with a commercially available DOX solution for injection (DOX-IN) and liposomal-DOX (DOX-MY). View Full-Text
Keywords: high-throughput analysis; doxorubicin metabolites; HPLC-FD method; validation; nanoformulation high-throughput analysis; doxorubicin metabolites; HPLC-FD method; validation; nanoformulation
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MDPI and ACS Style

Zorić, L.; Drinković, N.; Micek, V.; Frkanec, L.; Türeli, A.E.; Günday-Türeli, N.; Vinković Vrček, I.; Frkanec, R. High-Throughput Method for the Simultaneous Determination of Doxorubicin Metabolites in Rat Urine after Treatment with Different Drug Nanoformulations. Molecules 2022, 27, 1177. https://doi.org/10.3390/molecules27041177

AMA Style

Zorić L, Drinković N, Micek V, Frkanec L, Türeli AE, Günday-Türeli N, Vinković Vrček I, Frkanec R. High-Throughput Method for the Simultaneous Determination of Doxorubicin Metabolites in Rat Urine after Treatment with Different Drug Nanoformulations. Molecules. 2022; 27(4):1177. https://doi.org/10.3390/molecules27041177

Chicago/Turabian Style

Zorić, Lara, Nikša Drinković, Vedran Micek, Leo Frkanec, Akif Emre Türeli, Nazende Günday-Türeli, Ivana Vinković Vrček, and Ruža Frkanec. 2022. "High-Throughput Method for the Simultaneous Determination of Doxorubicin Metabolites in Rat Urine after Treatment with Different Drug Nanoformulations" Molecules 27, no. 4: 1177. https://doi.org/10.3390/molecules27041177

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