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


CONCLUSIONS
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.
Roche Pharmaceutical Research & Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland.
Katja
K
Heinig
Roche Pharmaceutical Research & Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland.
Denis
D
Herzog
Roche Pharmaceutical Research & Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland.
Luca
L
Ferrari
Roche Pharmaceutical Research & Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Grenzacherstrasse 124, 4070 Basel, Switzerland.
Daniela
D
Fraier
Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd., 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan.
Kazuhiro
K
Miya
Roche Pharmaceutical Research & Early Development, Clinical Pharmacology, Roche Innovation Center, New York, NY, USA.
Peter N
PN
Morcos
D002227:Carbazoles / Q000378:metabolism / Q000627:therapeutic use / Q000652:urine*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards; D006801:Humans; D010880:Piperidines / Q000378:metabolism / Q000627:therapeutic use / Q000652:urine*; D047428:Protein Kinase Inhibitors / Q000378:metabolism / Q000627:therapeutic use / Q000652:urine*; D011786:Quality Control; D053719:Tandem Mass Spectrometry / Q000379:methods* / Q000592:standards
D002227:Carbazoles; D010880:Piperidines; D047428:Protein Kinase Inhibitors; C582670:alectinib
alectinib; nonspecific binding; urine