Al-Hossaini Abdullah M, Darwish Hany W, Bakheit Ahmed H, Darwish Ibrahim A
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Pharmaceuticals (Basel). 2023 Sep 6;16(9):1260. doi: 10.3390/ph16091260.
Lorlatinib (LOR) is a third-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor drug. The Food and Drug Administration (FDA) has granted an approval for the use of LOR as a first therapeutic intervention for individuals diagnosed with ALK-positive metastatic and advanced non-small-cell lung cancer (NSCLC). The present study outlines, for the first time, the development and validation of an innovative microwell-based spectrofluorimetric (MW-SFL) method for the quantification of LOR. The proposed method involved the enhancement of the weak native fluorescence of LOR by its micellization into the sodium lauryl sulfate (SLS) micelles. The procedures of the method were conducted in white opaque plates with 96 microwells, and the enhanced fluorescence signals were measured by a fluorescence plate reader at 405 nm after excitation at 310 nm. The measured relative fluorescence intensity (RFI) had a linear relationship with LOR concentrations in the range of 60-1600 ng mL. The limit of detection (LOD) and the limit of quantification (LOQ) were found to be 19 and 56 ng mL, respectively. The method's accuracy and precision were assessed using a recovery study; the recovery values ranged from 99.98% to 101.40%, accompanied by relative standard deviation (RSD) values of 0.42% to 1.59%. The proposed MW-SFL method combined the advantages of the intrinsically high sensitivity of the spectrofluorimetric measurement and the excellent throughput of the microwell-based approach. The results proved the method is effective in the determination of LOR in its pharmaceutical tablets, tablet dissolution testing, as well as in spiked urine with a high degree of precision and accuracy. The MW-SFL method is notable for its simple procedures and utilization of water as a solvent, as well as minimal quantities of sample solutions. These features align with its ecofriendly approach to green chemistry principles. These advantages gave the proposed MW-SFL method a high potential value for the determination of LOR in clinical and quality control laboratories.
洛拉替尼（LOR）是一种第三代间变性淋巴瘤激酶（ALK）酪氨酸激酶抑制剂药物。美国食品药品监督管理局（FDA）已批准将LOR用作对诊断为ALK阳性转移性和晚期非小细胞肺癌（NSCLC）患者的首个治疗干预手段。本研究首次概述了一种用于定量LOR的基于微孔板的创新荧光光谱法（MW-SFL）的开发与验证。所提出的方法涉及通过将LOR胶束化到十二烷基硫酸钠（SLS）胶束中来增强其微弱的天然荧光。该方法的步骤在具有96个微孔的白色不透明板中进行，增强后的荧光信号在310nm激发后由荧光酶标仪在405nm处测量。测得的相对荧光强度（RFI）与LOR浓度在60 - 1600 ng/mL范围内呈线性关系。检测限（LOD）和定量限（LOQ）分别为19和56 ng/mL。使用回收率研究评估了该方法的准确性和精密度；回收率值范围为99.98%至101.40%，相对标准偏差（RSD）值为0.42%至1.59%。所提出的MW-SFL方法结合了荧光光谱测量固有的高灵敏度和基于微孔板方法的出色通量的优点。结果证明该方法在测定LOR的药物片剂、片剂溶出度测试以及加标尿液中具有高度的精密度和准确性。MW-SFL方法以其简单的程序、使用水作为溶剂以及最少的样品溶液用量而著称。这些特点符合其对绿色化学原则的环保方法。这些优点使所提出的MW-SFL方法在临床和质量控制实验室中具有很高的潜在价值。
