Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Medicina (Kaunas). 2024 Oct 14;60(10):1686. doi: 10.3390/medicina60101686.
Seliciclib (SEL) is the first selective, orally bioavailable potential drug containing cyclin-dependent kinase inhibitors. Preclinical studies showed antitumor activity in a broad range of human tumor xenografts, neurodegenerative diseases, renal dysfunctions, viral infections, and chronic inflammatory disorders. To support the pharmacokinetics and aid in therapeutic monitoring of SEL following its administration for therapy, an efficient analytical tool capable of quantifying the concentrations of SEL in blood plasma is needed. In the literature, there is no existing method for quantifying SEL in plasma samples. This study introduces the first HPLC method with a photodiode array (PDA) detector for the quantitation of SEL in plasma. The chromatographic resolution of SEL and linifanib as an internal standard (IS) was achieved on Zorbax Eclipse Plus C18 HPLC column (150 mm length × 4.6 mm internal diameter, 5 µm particle size), with a mobile phase composed of acetonitrile-ammonium acetate, pH 5 (50:50, /) at a flow rate of 1.0 mL min. Both SEL and IS were detected by PDA at 230 nm. The method was validated according to the ICH guidelines for bioanalytical method validation. The method exhibited linearity in concentrations ranging from 50 to 1000 ng mL, with a limit of quantitation of 66.1 ng mL. All remaining validation parameters satisfied the ICH validation criteria. The environmental sustainability of the method was verified using three extensive tools. The proposed HPLC-PDA method was effectively utilized to study the pharmacokinetics of SEL in rats after a single oral administration of 25 mg/kg. The proposed method stands as a valuable tool for studying SELs for pharmacokinetics in humans. It aids in achieving the targeted therapeutic advantages and safety of treatment with SEL by optimizing the SEL dosage and dosing schedule.
西利昔布（SEL）是首个选择性、口服生物可利用的潜在含细胞周期蛋白依赖性激酶抑制剂药物。临床前研究显示，其在广泛的人类肿瘤异种移植物、神经退行性疾病、肾功能障碍、病毒感染和慢性炎症性疾病中具有抗肿瘤活性。为支持 SEL 给药后用于治疗的药代动力学和辅助治疗监测，需要一种能够定量检测血浆中 SEL 浓度的高效分析工具。在文献中，目前尚无用于定量检测血浆中 SEL 浓度的方法。本研究介绍了首个用于定量检测血浆中 SEL 的 HPLC 方法，该方法配备有光电二极管阵列（PDA）检测器。SEL 和作为内标（IS）的利尼伐尼在 Zorbax Eclipse Plus C18 HPLC 柱（150mm 长度×4.6mm 内径，5µm 粒径）上实现色谱分离，流动相由乙腈-乙酸铵，pH5（50:50，/）组成，流速为 1.0mL min。SEL 和 IS 均通过 PDA 在 230nm 处检测。该方法按照 ICH 生物分析方法验证指南进行了验证。该方法在 50 至 1000ng mL 的浓度范围内呈线性，定量下限为 66.1ng mL。所有其余验证参数均满足 ICH 验证标准。该方法的环境可持续性使用三种扩展工具进行了验证。该 HPLC-PDA 方法在大鼠单次口服 25mg/kg 后成功用于研究 SEL 的药代动力学。该方法为研究 SEL 在人类中的药代动力学提供了有价值的工具。它通过优化 SEL 剂量和给药方案，有助于实现 SEL 治疗的靶向治疗优势和安全性。
