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

Zorić, Lara; Drinković, Nikša; Micek, Vedran; Frkanec, Leo; Türeli, Akif Emre; Günday-Türeli, Nazende; Vinković Vrček, Ivana; Frkanec, Ruža (2022) High-Throughput Method for the Simultaneous Determination of Doxorubicin Metabolites in Rat Urine after Treatment with Different Drug Nanoformulations. Molecules, 27 (4). ISSN 1420-3049

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Abstract

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).

Item Type: Article
Uncontrolled Keywords: High-throughput analysis ; Doxorubicin metabolites ; HPLC-FD method ; Validation ; Nanoformulation
Subjects: NATURAL SCIENCES > Chemistry
NATURAL SCIENCES > Interdisciplinary Natural Sciences
BIOMEDICINE AND HEALTHCARE > Basic Medical Sciences
INTERDISCIPLINARY AREAS OF KNOWLEDGE > Biotechnology in Biomedicine (natural science, biomedicine and healthcare, bioethics area
Divisions: Division of Organic Chemistry and Biochemistry
Projects:
Project titleProject leaderProject codeProject type
Sinteza supramolekulskih samo-udruženih nanostruktura za izgradnju naprednih funkcionalnih materijalaFrkanec, LeoIP-2018-01-6910HRZZ
Farmaceutski otvorena ispitna platforma za nano-farmaceutske inovativne proizvodeVinković Vrček, Ivana953110EK
Siguran pristup za razvoj nano-sustava za ciljanu isporuku lijekova u mozakVinković Vrček, IvanaPZS-2019-02-4323HRZZ
Depositing User: Sofija Konjević
Date Deposited: 10 Mar 2022 11:46
URI: http://fulir.irb.hr/id/eprint/7057
DOI: 10.3390/molecules27041177

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