Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Medicina (Kaunas). 2023 Oct 12;59(10):1813. doi: 10.3390/medicina59101813.
Ceritinib (CER) is a potent drug of the third-generation tyrosine kinase inhibitor class. CER has been approved for the treatment of patients with non-small-cell lung cancer (NSCLC) harboring the anaplastic lymphoma kinase (ALK) mutation gene. In the literature, there is no green and high-throughput analytical method for the quantitation of CER in its dosage form (Zykadia capsules). This study describes, for the first time, the development and validation of two novel one-step and green microwell spectrophotometric methods (MW-SPMs) for the high-throughput quantitation of CER in Zykadia capsules. These two methods were based on an formation of colored derivatives upon the reaction of CER with two different benzoquinone reagents via two different mechanisms. These reagents were -benzoquinone (OBQ) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), and their reactions proceeded via condensation and charge transfer reactions, respectively. The reactions were carried out in 96-well transparent plates, and the absorbances of the colored reaction products were measured with an absorbance microplate reader at 540 and 460 nm for reactions with OBQ and DDQ, respectively. The optimum conditions of reactions were established, their molar ratios were determined, and reaction mechanisms were postulated. Under the refined optimum reaction conditions, procedures of MW-SPMs were established and validated according to the guidelines of the International Council on Harmonization. The limits of quantitation were 6.5 and 10.2 µg/well for methods involving reactions with OBQ and DDQ, respectively. Both methods were applied with great reliability to the determination of CER content in Zykadia capsules and their drug uniformity. Greenness of the MW-SPMs was evaluated using three different metric tools, and the results proved that the two methods fulfil the requirements of green analytical approaches. In addition, the simultaneous handling of a large number of samples with microvolumes in the proposed methods gave them the advantage of a high-throughput analysis. : The two methods are valuable tools for rapid routine application in pharmaceutical quality control units for the quantitation of CER.
塞瑞替尼（CER）是一种第三代酪氨酸激酶抑制剂类药物。CER 已被批准用于治疗携带间变性淋巴瘤激酶（ALK）突变基因的非小细胞肺癌（NSCLC）患者。在文献中，尚无用于定量其剂型（Zykadia 胶囊）中 CER 的绿色高通量分析方法。本研究首次描述了两种新颖的一步法和绿色微孔板分光光度法（MW-SPM）的开发和验证，用于 Zykadia 胶囊中 CER 的高通量定量。这两种方法都是基于 CER 与两种不同的苯醌试剂通过两种不同的机制反应形成有色衍生物。这些试剂是邻苯醌（OBQ）和 2,3-二氯-5,6-二氰基-1,4-苯醌（DDQ），它们的反应分别通过缩合和电荷转移反应进行。反应在 96 孔透明板中进行，并用分光光度计在 540nm 和 460nm 处测量有色反应产物的吸光度，用于与 OBQ 和 DDQ 的反应。建立了最佳反应条件，确定了它们的摩尔比，并提出了反应机制。在最佳反应条件下，根据国际协调理事会的指南建立和验证了 MW-SPM 的程序。对于涉及与 OBQ 和 DDQ 反应的方法，定量限分别为 6.5 和 10.2μg/孔。两种方法都可可靠地用于 Zykadia 胶囊中 CER 含量及其药物均匀性的测定。使用三种不同的度量工具评估 MW-SPM 的绿色度，结果证明两种方法都符合绿色分析方法的要求。此外，所提出的方法中大量微体积样品的同时处理使它们具有高通量分析的优势。这两种方法是快速常规应用于药物质量控制单位用于 CER 定量的有价值工具。
