Department of Clinical Pharmacy, Oita University Hospital, Yufu-shi, Oita, Japan; and.
Department of Orthopaedic Surgery, Oita University Faculty of Medicine, Yufu-shi, Oita, Japan .
Ther Drug Monit. 2021 Jun 1;43(3):416-421. doi: 10.1097/FTD.0000000000000821.
Pazopanib is widely used to treat renal cell carcinomas and soft tissue tumors in Japan. Pazopanib has significant therapeutic efficacy but it is associated with frequent severe adverse effects. Therapeutic drug monitoring (TDM) may help to prevent adverse effects. A more convenient and rapid pazopanib assay is desirable for the application of TDM in clinical settings. In this study, the authors developed a high-throughput method for quantifying pazopanib in human plasma using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).
After a simple solid-phase extraction step using a 96-well plate, pazopanib was analyzed by UHPLC-MS/MS in the positive electrospray ionization mode.
The novel method fulfilled the requirements of the US Food and Drug Administration and the European Medicines Agency guidelines for assay validation, and the lower limit of quantification was 0.5 mcg/mL. The calibration curves were linear over the concentration range of 0.5-100 mcg/mL. The average recovery rate was 102.0% ± 3.9% (mean ± SD). The precision was below 5.0%, and the accuracy was within 12.0% for all quality control levels. Matrix effect varied between 90.9% and 97.1%. This assay was successfully applied to TDM of pazopanib trough concentrations in 3 patients treated with the drug for soft tissue tumors.
The authors succeeded in developing a novel high-throughput UHPLC-MS/MS method for quantifying pazopanib in human plasma. This method can be applied to TDM of patients receiving pazopanib in clinical settings.
帕唑帕尼在日本被广泛用于治疗肾细胞癌和软组织肿瘤。帕唑帕尼具有显著的治疗效果，但也与频繁发生的严重不良反应相关。治疗药物监测（TDM）可能有助于预防不良反应。对于 TDM 在临床环境中的应用，需要一种更方便、更快速的帕唑帕尼检测方法。在这项研究中，作者开发了一种使用超高效液相色谱-串联质谱（UHPLC-MS/MS）定量人血浆中帕唑帕尼的高通量方法。
采用 96 孔板固相萃取步骤后，采用正电喷雾电离模式的 UHPLC-MS/MS 分析帕唑帕尼。
该新方法满足美国食品和药物管理局和欧洲药品管理局分析验证指南的要求，定量下限为 0.5 mcg/mL。校准曲线在 0.5-100 mcg/mL 的浓度范围内呈线性。平均回收率为 102.0%±3.9%（平均值±SD）。所有质控水平的精密度均低于 5.0%，准确度均在 12.0%以内。基质效应在 90.9%-97.1%之间变化。该方法成功应用于 3 例软组织肿瘤患者接受帕唑帕尼治疗的药物谷浓度 TDM。
作者成功开发了一种用于定量人血浆中帕唑帕尼的新型高通量 UHPLC-MS/MS 方法。该方法可应用于临床环境中接受帕唑帕尼治疗的患者的 TDM。
