LC-MS/MS determination of alectinib and its major human metabolite M4 in human urine: prevention of nonspecific binding

Bioanalysis. 2017 Mar;9(5):459-468. doi: 10.4155/bio-2016-0284. Epub 2017 Feb 8.

Abstract

Aim: Alectinib (Alecensa®) is an anaplastic lymphoma kinase inhibitor for the treatment of anaplastic lymphoma kinase positive non-small-cell lung cancer, and M4 is its major pharmacologically active metabolite. To characterize the pharmacokinetics and excretion of alectinib and M4 in human urine, a bioanalytical method was required.

Results: An LC-MS/MS method using supported liquid extraction was developed for the determination of alectinib and M4 in human urine over the concentration range 0.5-500 ng/ml. Accuracy ranged from 92.0 to 112.2% and precision (CV) was below 9.6%.

Conclusion: The method was successfully employed to determine alectinib and M4 concentrations in urine samples from a clinical mass balance study. Addition of the surfactant Tween-20 to urine prevented nonspecific binding of the analytes.

Keywords: alectinib; nonspecific binding; urine.

MeSH terms

  • Carbazoles / metabolism
  • Carbazoles / therapeutic use
  • Carbazoles / urine*
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Chromatography, High Pressure Liquid / methods*
  • Chromatography, High Pressure Liquid / standards
  • Humans
  • Piperidines / metabolism
  • Piperidines / therapeutic use
  • Piperidines / urine*
  • Protein Kinase Inhibitors / metabolism
  • Protein Kinase Inhibitors / therapeutic use
  • Protein Kinase Inhibitors / urine*
  • Quality Control
  • Tandem Mass Spectrometry / methods*
  • Tandem Mass Spectrometry / standards

Substances

  • Carbazoles
  • Piperidines
  • Protein Kinase Inhibitors
  • alectinib