Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Medicina (Kaunas). 2024 Sep 29;60(10):1601. doi: 10.3390/medicina60101601.
: Uterine sarcoma, a rare cancer originating in the smooth muscle of the uterus, exhibits high rates of recurrence and metastasis. It represents one of the most challenging types of cancer due to its chemorefractory nature, showing little response to conventional chemotherapy methods and displaying a relative survival rate of 30-40%. A potentially promising approach for treating uterine sarcoma involves combination therapy with paclitaxel (PAC), a microtubule-targeting agent, and seliciclib (SEL), a cyclin-dependent kinase inhibitor. SEL has been identified as a drug that can enhance the effectiveness of PAC through synergistic effects. To further refine this treatment strategy, an efficient analytical tool capable of simultaneously measuring the concentrations of PAC and SEL in blood plasma is needed. This tool would make it easier to study the pharmacokinetic interactions of potential drugs and assist in monitoring therapy when administering this combination treatment. Regrettably, a method meeting these specific requirements has not been documented in the existing literature. : This article introduces the first HPLC technique employing a PDA detector to concurrently measure PAC and SEL levels in plasma. The methodology underwent validation in accordance with the ICH standards for validating bioanalytical methods. : The method exhibited linearity in the concentrations ranging from 0.8 to 100 µg mL for both PAC and SEL. The limits of quantification were determined and found to be 1.34 and 1.25 µg mL for PAC and SEL, respectively. All the other validation criteria conformed to the ICH validation standards. The HPLC-PDA method was successfully employed to quantify both PAC and SEL in plasma samples with a high level of reliability (in terms of accuracy and precision). The eco-friendliness of the approach was verified using three thorough assessments. This technique serves as a valuable asset in establishing the correct dosage and administration schedule for the combined treatment involving PAC and SEL, ensuring the desired therapeutic effects and safety in managing uterine sarcoma. : The proposed HPLC-PDA method is the first reliable and eco-friendly method developed to simultaneously determine PAC and SEL in high-throughput plasma samples in clinical laboratories.
: 子宫肉瘤是一种罕见的癌症，起源于子宫的平滑肌，具有很高的复发和转移率。由于其化疗耐药性，它是最具挑战性的癌症类型之一，对常规化疗方法反应不大，相对存活率为 30-40%。一种有前途的治疗子宫肉瘤的方法是联合使用紫杉醇（PAC）和塞利昔布（SEL），紫杉醇是一种微管靶向药物，塞利昔布是一种细胞周期蛋白依赖性激酶抑制剂。SEL 已被确定为一种可以通过协同作用提高 PAC 效果的药物。为了进一步完善这种治疗策略，需要一种能够同时测量血浆中 PAC 和 SEL 浓度的高效分析工具。这种工具将使研究潜在药物的药代动力学相互作用变得更加容易，并在联合治疗时有助于监测治疗效果。遗憾的是，现有的文献中没有记录满足这些特定要求的方法。 : 本文介绍了一种使用 PDA 检测器同时测量血浆中 PAC 和 SEL 浓度的 HPLC 技术。该方法按照 ICH 验证生物分析方法的标准进行了验证。 : 该方法在 PAC 和 SEL 的浓度范围为 0.8 至 100 µg mL 时表现出线性。定量限分别确定为 PAC 和 SEL 的 1.34 和 1.25 µg mL。所有其他验证标准均符合 ICH 验证标准。该 HPLC-PDA 方法成功地用于定量分析血浆样品中的 PAC 和 SEL，具有很高的可靠性（在准确性和精密度方面）。该方法的环保性通过三次全面评估得到了验证。该技术在建立 PAC 和 SEL 联合治疗的正确剂量和给药方案方面具有重要价值，可确保在治疗子宫肉瘤时达到预期的治疗效果和安全性。 : 所提出的 HPLC-PDA 方法是第一个可靠且环保的方法，可用于在临床实验室中同时测定高通量血浆样品中的 PAC 和 SEL。
