LC–MS/MS Determination of Alectinib and its Major Human Metabolite M4 in Human Urine: Prevention of Nonspecific Binding

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

Supplementary Data

Financial & competing interests disclosure

All authors are employed by F Hoffmann-La Roche Ltd or Chugai Pharmaceutical Co., Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. Informed consent has been obtained from all individuals who participated in the clinical trial.

Acknowledgements

The authors are thankful to Q2 Solutions, a Quintiles Quest Joint Venture, for support in method validation and samples analysis. We thank Julian Potter for his thorough independent review of the manuscript.