ceritinib and nintedanib

Multiple small-molecule kinase inhibitors with specific molecular targets have recently been developed for the treatment of cancer. This article reports the development and validation of an ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method to simultaneously analyse the small-molecule kinase inhibitors dacomitinib, ceritinib, lorlatinib, and nintedanib in human plasma. For chromatographic analyte separation, an Acquity UPLC® BEH C18 column 1.7 μm, 50 mm x 2.1 mm was used with a binary gradient of pure water/formic acid/ammonium formate (100:0.1:0.02, v/v/v) and methanol/formic acid (100:0.1, v/v). Calibration curves for all small-molecule kinase inhibitors were 5.00-500 ng/mL. Validation of this method met all requirements of the Food and Drug administration. Additionally, clinical applicability was demonstrated by quantification of multiple samples from a pharmacokinetic study in patients with lung cancer.

Topics: Aminopyridines; Chromatography, High Pressure Liquid; Chromatography, Liquid; Humans; Indoles; Lactams; Lactams, Macrocyclic; Pyrazoles; Pyrimidines; Quinazolinones; Reproducibility of Results; Sulfones; Tandem Mass Spectrometry

Topics: Antibodies, Monoclonal; Antineoplastic Agents; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Docetaxel; Erlotinib Hydrochloride; Female; Humans; Imidazoles; Indoles; Lung Neoplasms; Male; Medical Oncology; Multicenter Studies as Topic; Oximes; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Quinazolines; Randomized Controlled Trials as Topic; Small Cell Lung Carcinoma; Societies, Medical; Sulfones; Sunitinib; Taxoids; Treatment Outcome; Triazoles; United States