A Novel Quantum Dots-Based Fluorescent Sensor for Determination of the Anticancer Dacomitinib: Application to Dosage Forms

Molecules. 2023 Mar 3;28(5):2351. doi: 10.3390/molecules28052351.

Abstract

One of the most promising drugs recently approved for the treatment of various types of cancer is dacomitinib, which belongs to the tyrosine kinase inhibitor class. The US Food and Drugs Administration (FDA) has recently approved dacomitinib as a first-line treatment for patients suffering from non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. The current study proposes the design of a novel spectrofluorimetric method for determining dacomitinib based on newly synthesized nitrogen-doped carbon quantum dots (N-CQDs) as fluorescent probes. The proposed method is simple and does not require pretreatment or preliminary procedures. Since the studied drug does not have any fluorescent properties, the importance of the current study is magnified. When excited at 325 nm, N-CQDs exhibited native fluorescence at 417 nm, which was quantitatively and selectively quenched by the increasing concentrations of dacomitinib. The developed method involved the simple and green microwave-assisted synthesis of N-CQDs, using orange juice as a carbon source and urea as a nitrogen source. The characterization of the prepared quantum dots was performed using different spectroscopic and microscopic techniques. The synthesized dots had consistently spherical shapes and a narrow size distribution and demonstrated optimal characteristics, including a high stability and a high fluorescence quantum yield (25.3%). When assessing the effectiveness of the proposed method, several optimization factors were considered. The experiments demonstrated highly linear quenching behavior across the concentration range of 1.0-20.0 μg/mL with a correlation coefficient (r) of 0.999. The recovery percentages were found to be in the range of 98.50-100.83% and the corresponding relative standard deviation (%RSD) was 0.984. The proposed method was shown to be highly sensitive with a limit of detection (LOD) as low as 0.11 μg/mL. The type of mechanism by which quenching took place was also investigated by different means and was found to be static with a complementary inner filter effect. For quality purposes, the assessment of the validation criteria adhered to the ICHQ2(R1) recommendations. Finally, the proposed method was applied to a pharmaceutical dosage form of the drug (Vizimpro® Tablets) and the obtained results were satisfactory. Considering the eco-friendly aspect of the suggested methodology, using natural materials to synthesize N-CQDs and water as a diluting solvent added to its greenness profile.

Keywords: dacomitinib; fluorescence; nitrogen-doped carbon quantum dots; quenching; sensor.

MeSH terms

  • Carbon / chemistry
  • Carcinoma, Non-Small-Cell Lung*
  • Fluorescent Dyes / chemistry
  • Humans
  • Lung Neoplasms*
  • Nitrogen / chemistry
  • Quantum Dots* / chemistry
  • Spectrometry, Fluorescence / methods

Substances

  • dacomitinib
  • Fluorescent Dyes
  • Carbon
  • Nitrogen