Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Department of Analytical Chemistry, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo 11562, Egypt.
Molecules. 2023 May 1;28(9):3852. doi: 10.3390/molecules28093852.
Lorlatinib (LRL) is the first drug of the third generation of anaplastic lymphoma kinase (ALK) inhibitors used a first-line treatment of non-small cell lung cancer (NSCLC). This study describes, for the first time, the investigations for the formation of a charge transfer complex (CTC) between LRL, as electron donor, with chloranilic acid (CLA), as a π-electron acceptor. The CTC was characterized by ultraviolet (UV)-visible spectrophotometry and computational calculations. The UV-visible spectrophotometry ascertained the formation of the CTC in methanol via formation of a new broad absorption band with maximum absorption peak (λmax) at 530 nm. The molar absorptivity (ε) of the complex was 0.55 × 10 L mol cm and its band gap energy was 2.3465 eV. The stoichiometric ratio of LRL/CLA was found to be 1:2. The association constant of the complex was 0.40 × 10 L mol, and its standard free energy was -0.15 × 10 J mole. The computational calculation for the atomic charges of an energy minimized LRL molecule was conducted, the sites of interaction on the LRL molecule were assigned, and the mechanism of the reaction was postulated. The reaction was adopted as a basis for developing a novel 96-microwell spectrophotometric method (MW-SPA) for LRL. The assay limits of detection and quantitation were 2.1 and 6.5 µg/well, respectively. The assay was validated, and all validation parameters were acceptable. The assay was implemented successfully with great precision and accuracy to the determination of LRL in its bulk form and pharmaceutical formulation (tablets). This assay is simple, economic, and more importantly has a high-throughput property. Therefore, the assay can be valuable for routine in quality control laboratories for analysis of LRL's bulk form and pharmaceutical tablets.
洛拉替尼（LRL）是第三代间变性淋巴瘤激酶（ALK）抑制剂中的第一种药物，用于非小细胞肺癌（NSCLC）的一线治疗。本研究首次描述了 LRL（电子供体）与氯代邻苯二甲酸（CLA，π-电子受体）之间形成电荷转移复合物（CTC）的研究。通过紫外可见分光光度法和计算计算对 CTC 进行了表征。紫外可见分光光度法通过在甲醇中形成新的宽吸收带，最大吸收峰（λmax）为 530nm，确证了 CTC 的形成。配合物的摩尔吸光率（ε）为 0.55×10 L mol cm，带隙能为 2.3465eV。确定 LRL/C LA的摩尔比为 1:2。该配合物的缔合常数为 0.40×10 L mol，标准自由能为-0.15×10 J mole。对能量最小化的 LRL 分子的原子电荷进行了计算计算，分配了 LRL 分子上的相互作用部位，并提出了反应的机理。该反应被采用作为开发用于测定 LRL 的新型 96 微孔分光光度法（MW-SPA）的基础。检测限和定量限分别为 2.1 和 6.5μg/孔。对该方法进行了验证，所有验证参数均可接受。该方法成功地用于测定 LRL 的散装形式和药物制剂（片剂），具有很高的精密度和准确性。该方法简单，经济，更重要的是具有高通量的特性。因此，该方法对于常规质量控制实验室分析 LRL 的散装形式和药物片剂具有重要价值。
