ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Drug Metabolism and Transport
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1510583
Liquid chromatography tandem mass spectrometry assay for the simultaneous determination of apalutamide and its active metabolite N-desmethyl apalutamide, and application in real world patients with castration-resistant prostate cancer
Provisionally accepted
- 1Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China
- 2Second People’s Hospital of Yibin, Yibin, China
- 3Chengdu Second People's Hospital, Chengdu, Sichuan Province, China
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Background 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 Methods 24 patients diagnosed with desmoplasia-resistant prostate cancer (NM-CRPC) were recruited. Blood samples were drawn after 4 weeks' administration with apalutamide at a dose of 180 mg once daily to ensure steady state blood levels.were achieved. Apalutamide and N-desmethyl apalutamide were analyzed 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 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.Conclusions Therapeutic drug monitoring can help evaluate the individual differences between patients taking apalutamide. A dose of 180 mg could reduce baseline PSA level significantly (p < 0.05), and the incidence of skin rash was less compared to a dose of 240mg.
Keywords: Apalutamide, N-desmethyl apalutamide, Therapeutic drug monitoring, LC-MS/MS, castration-resistant prostate cancer, human plasma
Received: 14 Oct 2024; Accepted: 16 Apr 2025.
Copyright: © 2025 Zhu, Chen, Chen, Yang, Zhang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jun Li, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, China
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