A simple HPLC-UV method for quantification of enzalutamide and its active metabolite N-desmethyl enzalutamide in patients with metastatic castration-resistant prostate cancer

Enzalutamide is currently approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). To date, a single liquid chromatographic-tandem mass spectroscopy method is available to measure plasma enzalutamide concentrations in mCRPC patients. In this work, an accurate and sensitive HPLC-UV method has been developed for the simultaneous determination of enzalutamide and its active metabolite, N-desmethyl enzalutamide in plasma from mCRPC patients. Before precipitation of proteins with acetonitrile, samples were spiked with nilutamide (internal standard). Separation of analytes was achieved under isocratic elution on a C18 Kinetex column. The mobile phase consisted of a mixture of ammonium acetate buffer (pH=4.6, 20mM) and acetonitrile (60:40, v/v), and was delivered at a flow rate of 1.5mL/min throughout a 9-min run. UV detection was performed at 270nm. The method was linear over a concentration range of 0.50-50.0μg/mL for both analytes. Within- and between-day imprecision and accuracy were ≤10% at concentrations 0.75, 5.00, and 50.0μg/mL. This method has been implemented to assay steady-state trough plasma concentrations (n=30) of enzalutamide and N-desmethyl enzalutamide in 16 mCRPC patients. Overall, this HPLC-UV method is well-suited for routine application in clinical laboratories to perform therapeutic drug monitoring of enzalutamide in mCRPC patients.

Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 2017 Apr 05 [Epub ahead of print]

Alicja Puszkiel, Alain Plé, Olivier Huillard, Gaëlle Noé, Constance Thibault, Stéphane Oudard, François Goldwasser, Michel Vidal, Jérome Alexandre, Benoit Blanchet

Department of Pharmacokinetics and Pharmacochemisty, Hôpital Cochin, AP-HP, Paris, France., Department of Medical Oncology, Hôpital Cochin, AP-HP, Paris, France; Université Paris Descartes, CARPEM, Paris, France., Department of Pharmacokinetics and Pharmacochemisty, Hôpital Cochin, AP-HP, Paris, France; UMR8638 CNRS, Faculté de Pharmacie de Paris, Université Paris Descartes, PRES Sorbonne Paris Cité, Paris, France., Université Paris Descartes, CARPEM, Paris, France; Department of Medical Oncology, Hôpital Européen Georges Pompidou, AP-HP, Paris, France., Department of Medical Oncology, Hôpital Européen Georges Pompidou, AP-HP, Paris, France., Department of Medical Oncology, Hôpital Cochin, AP-HP, Paris, France; Université Paris Descartes, CARPEM, Paris, France; U1016 INSERM, UMR 8104 CNRS, UMR-S1016, Université Paris Descartes, Sorbonne Paris Cité, Paris, France., Department of Pharmacokinetics and Pharmacochemisty, Hôpital Cochin, AP-HP, Paris, France. Electronic address: .