Testing brigatinib in an oncological patient's hair: Evaluation of the time of disappearance after discontinuation and interpretation of concentrations obtained in regrowing hair after total loss.

Brigatinib (Alungrib®) is a next-generation anaplastic lymphoma kinase (ALK) inhibitor used for the treatment of ALK-rearranged non-small-cell lung cancer (NSCLC). While its quantification in blood and urine is well-documented, no study has investigated its incorporation in hair. Given the long-term administration of brigatinib, hair analysis could provide a valuable tool obtaining an historical profile of drug concentrations. This study presents the first reported case of brigatinib detection in hair, analyzing the hair of an oncological subject who experienced total hair loss due to chemotherapy followed by hair regrowth. The investigation of brigatinib was performed on a 31 cm long strand of hair belonging to a subject who had been on brigatinib treatment for more than 3 years. Hair was analyzed following decontamination with dichloromethane, incubation in basic buffer in the presence of 2 ng MDMA-D5 and liquid-liquid extraction using a new method developed on a liquid chromatography- tandem mass spectrometry system. With a limit of quantification determined at 1 pg/mg, the method was applied to 31 × 1 cm hair segments. Brigatinib was detected in all 31 hair segments, with concentrations varying over time (8-97 pg/mg) and peaking 22 months after hair regrowth. Despite a quite stable drug dosage, brigatinib levels fluctuated, suggesting an influence of chemotherapy-induced hair alterations on drug incorporation. Moreover, brigatinib remained detectable in hair up to eight months after treatment discontinuation.