Near-infrared carbon dots enable ultra-sensitive fluorometric detection of belzutifan: a novel approach for real-time therapeutic drug monitoring in cancer treatment

  • Anal Methods. 2025 Dec 11;17(48):9887-9897. doi: 10.1039/d5ay01670c.
Mohamed N Goda  1 ,  Laila S Alqarni  1 ,  K S Al-Namshah  1 ,  Hossieny Ibrahim  2 ,  Mohamed M El-Wekil  3 ,  Ramadan Ali  4 ,  Al-Montaser Bellah H Ali  3
Affiliations
  • 1. Department of Chemistry, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia.
  • 2. Department of Chemistry, Faculty of Science, Assiut University, Assiut 71516, Egypt.
  • 3. Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Assiut University, Assiut, Egypt. [email protected].
  • 4. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia.
PMID: 41347412 DOI: 10.1039/d5ay01670c
Abstract

Belzutifan, a hypoxia-inducible factor-2α (HIF-2α) inhibitor, represents a breakthrough therapeutic agent for treating von Hippel-Lindau disease-associated tumors and advanced renal cell carcinoma, necessitating precise therapeutic drug monitoring. This work presents the first application of near-infrared carbon dots (NIR-CDs) for belzutifan detection utilizing a dual-mechanism approach combining aggregation-induced quenching and inner filter effect for enhanced analytical performance. The NIR-CDs were synthesized from sulfosalicylic acid and ethylenediamine precursors, exhibiting strong near-infrared emission at 750 nm upon 290 nm excitation with excellent photostability and pH tolerance. The developed fluorometric sensor demonstrated outstanding analytical performance with a linear detection range of 5.0-130.0 ng mL-1 and a limit of detection of 1.35 ng mL-1, which is approximately 103 to 104 times lower than therapeutic plasma concentrations. Plasma sample analysis showed excellent extraction recovery ranging from 96.6% to 98.1% across three concentration levels with relative standard deviations below 4.27%. The method demonstrated successful clinical validation through analysis of plasma samples from rats, achieving excellent correlation with reference LC-MS/MS methods while providing real-time therapeutic drug monitoring capabilities. This represents the first fluorometric approach for belzutifan quantification and establishes a new paradigm for Anticancer drug monitoring that combines the advantages of carbon dot nanotechnology with clinically relevant near-infrared detection, offering significant potential for point-of-care therapeutic drug monitoring in oncology practice.

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