Akademik Veri Yönetim Sistemi
Microchemical Journal, cilt.215, 2025 (SCI-Expanded)
Breast cancer is one of the most frequent cancers in women worldwide, and it can efficiently be treated with doxorubicin (DOX), an anthracycline, cytotoxic antibiotic, and anticancer drug derived from the Streptomyces peucetus var.caesius bacteria. Here, a pretreatment-free, fully automated on-line SPE-LC-FL method was developed and validated for the quantification of DOX and its active metabolite doxorubicinol (DOXol) simultaneously in spiked human plasma samples and applied to real patient samples. A Zorbax Rx-C18 (4.6 × 150.0 mm, 3.5 μm) and a self-packed SPE column (20.0 × 1.0 mm i.d.) with ADS C4 material were used for separation and extraction, respectively. A gradient elution was executed at 1.0 mL/min using acetonitrile, 10 mM o-phosphoric acid, and ultra-pure water solutions as the mobile phase, detecting DOX and DOXol at λex 478 and λem 510 nm. The method exhibited a linearity range between 25.00 and 1500.00 ng/mL, with correlation coefficients of 0.9982 for DOX and 0.992 for DOXol. Lower range limit verification (QL/DL) for DOX was determined to be 15.00 ng/mL and 5.00 ng/mL, respectively, and for DOXol, it was 15.00 ng/mL and 5.00 ng/mL, respectively. Recoveries were ≥ 98.07 % and ≥ 76.94 %, and the relative standard deviations were ≤ 5 % for DOX and DOXol, respectively. The developed method was also successfully applied to the pharmacokinetic studies performed by using 3 different patient plasma samples obtained in 24 h. Cmax parameters of DOX and DOXol after i.v. (short-term infusion) administration were calculated between 978.58 and 1109.63 ng/mL and 30.26–118.11 ng/mL, respectively. The AGREE score was calculated as 0.74 over 1.0, confirming the method's greenness, while the use of a fully automated analytical system ensured compliance with four out of five key sustainability principles—replacement, reduction, reuse, and repurposing—thereby reinforcing the overall sustainability of the approach. Here we present a selective and sensitive study that enables a direct determination of DOX and DOXol in real plasma samples without the need for pretreatment.