Pharmaceutical Chemistry Department, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
Pharmaceutical Chemistry Department, College of Pharmacy, Prince Sattam bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.
Spectrochim Acta A Mol Biomol Spectrosc. 2023 Nov 5;300:122914. doi: 10.1016/j.saa.2023.122914. Epub 2023 May 26.
Recently, the kinase receptor inhibitor drug larotrectinib has been approved as a monotherapy for the treatment of patients with solid tumors containing the neurotrophic receptor tyrosine kinase gene fusion. In this paper, a novel sensitive spectrofluorimetric method was proposed for the determination of larotrectinib based on nitrogen-doped carbon quantum dots (N-CQDs) fluorescent probes. The proposed method is the first spectroscopic method for analysis of the cited drug, which is simple to implement and involves no pre-treatment steps or complicated techniques. The N-CQDs synthesis was performed by adopting a straightforward, fast, and environmentally friendly approach. It was achieved by means of a standard domestic microwave with inexpensive and readily available starting materials: orange juice (carbon source) and urea (nitrogen source). The synthesized N-CQDs were subjected to microscopic and spectroscopic characterization procedures. They were found to be stable with a sufficiently high fluorescence quantum yield (25.3%) and a small particle size distribution (2-5 nm). The motivation for the use of N-CQDs in this study arose from their excellent fluorescence intensities at 417 nm when excited at 325 nm. Larotrectinib was found to have a quantitative and selective quenching effect on the QDs fluorescence allowing for its sensitive determination. The drug's quenching mechanism was investigated and found to be of the static type. Under optimal conditions, the proposed approach permitted the determination of larotrectinib over the concentration interval of 5.0-28.0 µg/mL. The method showed sufficient sensitivity with a detection limit of 0.19 µg/mL and a quantitation limit of 0.57 µg/mL, enabling the determination of LARO in spiked human plasma samples. The approach's recovery percentage was found to be in the range of 99.09-100.73% for pure samples and 97.35-102.59% for plasma samples. The study also successfully applied the proposed approach to the commercial oral solution form of larotrectinib (Vitrakvi®) with high selectivity. Method greenness was further evaluated by adopting two metric tools, including the complementary green analytical procedure index (ComplexGAPI) and Analytical GREENNESS metric approach (AGREE), and it was confirmed to be excellent green. The proposed method was validated in accordance with the ICHQ2 (R1) recommendations and is considered an excellent candidate for potential application in the therapeutic monitoring of larotrectinib.
最近，激酶受体抑制剂药物拉罗替尼已被批准作为一种单药疗法，用于治疗含有神经营养受体酪氨酸激酶基因融合的实体肿瘤患者。本文提出了一种基于氮掺杂碳量子点（N-CQDs）荧光探针测定拉罗替尼的新型灵敏分光光度法。该方法是分析该药物的第一种光谱方法，简单易行，无需预处理步骤或复杂技术。N-CQDs 的合成采用简单、快速、环保的方法，在标准国产微波炉中，使用廉价易得的起始原料：橙汁（碳源）和尿素（氮源）。合成的 N-CQDs 经过微观和光谱特征分析。结果表明，它们具有足够高的荧光量子产率（25.3%）和较小的粒径分布（2-5nm），稳定性良好。本研究选择使用 N-CQDs 的原因是它们在 325nm 激发下在 417nm 处具有优异的荧光强度。拉罗替尼对 QDs 荧光具有定量和选择性猝灭作用，可对其进行灵敏测定。研究了药物的猝灭机制，发现为静态类型。在最佳条件下，该方法允许在 5.0-28.0μg/mL 的浓度范围内测定拉罗替尼。该方法具有足够的灵敏度，检测限为 0.19μg/mL，定量限为 0.57μg/mL，可用于测定加标人血浆样品中的 LARO。该方法的回收率在纯样品中为 99.09-100.73%，在血浆样品中为 97.35-102.59%。该研究还成功地将所提出的方法应用于拉罗替尼的商业口服溶液形式（Vitrakvi®），具有高选择性。通过采用两种度量工具，包括互补绿色分析程序指数（ComplexGAPI）和分析绿色度度量方法（AGREE），进一步评估了方法的绿色性，结果证实其具有优异的绿色性。该方法按照 ICHQ2（R1）建议进行了验证，被认为是拉罗替尼治疗监测中潜在应用的优秀候选方法。
