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 | ||||||||||||||||
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| 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 |
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| Divisions: | Division of Organic Chemistry and Biochemistry | ||||||||||||||||
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| Depositing User: | Leo Frkanec | ||||||||||||||||
| Date Deposited: | 10 Mar 2022 11:46 | ||||||||||||||||
| URI: | http://fulir.irb.hr/id/eprint/7057 | ||||||||||||||||
| DOI: | 10.3390/molecules27041177 |
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