Zhu Yuxuan, Chen Lu, Cheng Wenqiang, Yang Dingyuan, Zhang Lijuan, Li Jun
Department of Pharmacy, Personalized Drug Therapy Key Laboratory of Sichuan Province, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
Guanghan People's Hospital, Guanghan, China.
Front Pharmacol. 2025 May 19;16:1510583. doi: 10.3389/fphar.2025.1510583. eCollection 2025.
Apalutamide is used in the treatment of castration-resistant prostate cancer. A simple, specific, selective, and effective liquid chromatography-tandem mass spectrometry method for quantifying apalutamide and its active metabolite concentration in human plasma was developed and validated according to the FDA and EMA validation guidelines.
A total of 24 patients diagnosed with desmoplasia-resistant prostate cancer (NM-CRPC) were recruited. Blood samples were drawn after 4 weeks' administration of apalutamide at a dose of 180 mg once daily to ensure steady-state blood levels were achieved. Apalutamide and N-desmethyl apalutamide were analysed by quantitative liquid chromatography tandem mass spectrometry to measure the concentrations among individuals and the effect on the baseline level of prostate-specific antigen (PSA) and adverse events.
The linear range, precision, accuracy, matrix effect, recovery, carryover, and stability were appropriate according to the FDA and EMA validation guidelines. The apalutamide blood concentration range of the 24 patients was 0.517-7.27 μg/mL, and the median value was 4.92 μg/mL. The N-desmethyl apalutamide blood concentration range was 1.78-8.32 μg/mL, and the median value was 5.71 μg/mL. The median serum PSA level decreased from 61.03 (range 0.57-885.93) ng/mL at baseline to 0.970 (range 0.01-47.9) ng/mL at week 4.
Therapeutic drug monitoring can help evaluate the individual differences between patients taking apalutamide. A dose of 180 mg could reduce the baseline PSA level significantly (p < 0.05), and the incidence of skin rash was less compared to that of a dose of 240 mg.
阿帕鲁胺用于治疗去势抵抗性前列腺癌。根据美国食品药品监督管理局（FDA）和欧洲药品管理局（EMA）的验证指南，开发并验证了一种简单、特异、选择性强且有效的液相色谱-串联质谱法，用于定量测定人血浆中阿帕鲁胺及其活性代谢物的浓度。
共招募了24例诊断为去势抵抗性前列腺癌（NM-CRPC）的患者。在每天一次给予180 mg阿帕鲁胺4周后采集血样，以确保达到稳态血药浓度。采用定量液相色谱串联质谱法分析阿帕鲁胺和N-去甲基阿帕鲁胺，以测量个体间的浓度以及对前列腺特异性抗原（PSA）基线水平和不良事件的影响。
根据FDA和EMA验证指南，线性范围、精密度、准确度、基质效应、回收率、残留和稳定性均符合要求。24例患者的阿帕鲁胺血药浓度范围为0.517 - 7.27 μg/mL，中位数为4.92 μg/mL。N-去甲基阿帕鲁胺血药浓度范围为1.78 - 8.32 μg/mL，中位数为5.71 μg/mL。血清PSA水平中位数从基线时的61.03（范围0.57 - 885.93）ng/mL降至第4周时的0.970（范围0.01 - 47.9）ng/mL。
治疗药物监测有助于评估服用阿帕鲁胺患者之间的个体差异。180 mg剂量可显著降低基线PSA水平（p < 0.05），且与240 mg剂量相比，皮疹发生率更低。
