Quantitation of sunitinib, an oral multitarget tyrosine kinase inhibitor, and its metabolite in urine samples by nonaqueous capillary electrophoresis time of flight mass spectrometry

Abstract

A rapid, sensitive, and specific method was developed and validated using a nonaqueous-capillary electrophoresis method with TOF-MS for determination of sunitinib and N-desethyl sunitinib in human urine. In order to avoid ionic suppression a urine samples dilution with methanol 1:10 previous step was used. This was the only treatment step to urine samples before the injection. Despite this dilution of the urine, the detection limit was as low as 0.07 mg/L for sunitinib and 0.15 mg/L for N-desethyl sunitinib. Separation of compounds was achieved with a mixture of 5 mM ammonium formate in methanol. The calibration curves were linear over the range of 0.5-50.0 mg/L for the two analyzed compounds. The within-run and between-run precisions were within 5%, while the accuracy ranged from 96.0 to 100.4%. This method can be used in routine clinical practice to monitor sunitinib and N-desethyl sunitinib drugs in the urine of cancer patients treated with once daily administration.

Antineoplastic drugs and their analysis: a state of the art review

“…Sunitinib and its main metabolites in urine were finally analysed by NACE-MS after a simple one-tenth dilution of the sample at concentrations between 0.5 and 50 µg mL −1 . 560 …”

Recent advances in CE‐MS coupling: Instrumentation, methodology, and applications

“…Rodriguez et al. presented a quantitation of sunitinib, an oral multitarget tyrosine kinase inhibitor, and its metabolite in urine samples by nonaqueous CE‐TOF‐MS . Sunitinib, a drug for the treatment of renal cell carcinoma and gastrointestinal stromal tumor, was detected with LOD as low as 0.07 mg/L in urine diluted with methanol 1:10.…”

Determination of Tyrosine Kinase Inhibitors via Capillary Electrophoresis with Tandem Mass Spectrometry and Online Stacking Preconcentration

“…This problem can be overcome by using different type of detection, such as mass spectrometry (which also offers identification of the compounds of interest), or by using offline or online preconcentration techniques. Here, Rodriguez et al [ 36 ] achieved a 70 ng·mL −1 LOD for sunitinib using CE connected to TOF-MS. Forough et al [ 37 ] used nanocomposite-based electromembrane extraction followed by field-amplified sample injection online preconcentration in CE with UV detection, resulting in a determination of imatinib with an LOD of 6.24 ng·mL −1 . Nanomaterials, especially multi-walled carbon nanotubes, were also used for dispersive solid-phase extraction prior to CE-UV of dabrafenib and trametinib in serum samples (with LODs from 8 ng·mL −1 ) [ 38 ].…”