A simple HPLC-UV method for quantification of enzalutamide and its active metabolite N-desmethyl enzalutamide in patients with metastatic castration-resistant prostate cancer
2017
Puszkiel, Alicja | Plé, Alain | Huillard, Olivier | Noé, Gaëlle | Thibault, Constance | Oudard, Stéphane | Goldwasser, François | Vidal, Michel | Alexandre, Jérôme | Blanchet, Benoit
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.
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