Solid phase extraction prior to non-aqueous capillary electrophoresis with ultraviolet detection as a valuable strategy for therapeutic drug monitoring of cabozantinib

Abstract

Solid phase extraction (SPE) prior to non-aqueous capillary electrophoresis (NACE) with ultraviolet detection was used for the first time for the determination of cabozantinib (CBZ), the main drug used for the treatment of metastatic renal cancer, in urine. SPE was carried out in commercial C18 cartridges loaded with 8 mL of urine. Tamoxifen (TAM) was added as internal standard. After removal of the matrix with 8 mL of phosphate buffer (pH 7.0; 10 mM), 7 mL of MeOH:H2O (30:70; v/v) and 0.5 mL of MeOH, CBZ and TAM were eluted with 1.5 mL of methanol. The eluate was evaporated to dryness and reconstituted in background electrolyte (BGE). The CE method was carried out in a fused silica capillary (30 cm × 75 µm i.d.) at 19 °C at 10 kV with a BGE consisting of ammonium acetate (pH 7.0; 8 mM) containing 3 % acetic acid (v/v) in methanol.The preconcentration factor achieved was 5.3, and the limits of detection and quantification were 3.7 and 12 µg/L in urine, respectively. Linearity was observed up to 950 µg/L. Intra-day precision at 20, 400, and 850 µg/L of CBZ (n = 8) was below 10 % in peak areas. As for inter-day precision, no statistical differences were found in two consecutive days, according to the Snedecor “F” test (p > 0.05). Recovery studies in spiked urine samples ranged from 91.4 to 116.6 %.The present method was applied to samples from a patient under treatment with CBZ for metastatic renal cancer as an alternative to the current strategies for therapeutic drug monitoring.