A sensitive LC-MS-MS assay for the determination of lapatinib in human plasma in subjects with end-stage renal disease receiving hemodialysis

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 1097-1098; pp. 74 - 82
• Main Authors: Kocan, Geralyn P., Huang, Mike (Qingtao), Li, Fumin, Pai, Sudhakar
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.10.2018
• Subjects: drugs; End-stage renal disease; enzyme inhibitors; hemodialysis; Human plasma; humans; isotope labeling; kidney diseases; Lapatinib; LC-MS-MS; liquid chromatography; monitoring; neoplasms; patients; tandem mass spectrometry; tyrosine; End-stage renal disease; Human plasma; Lapatinib; LC-MS-MS
• ISSN: 1570-0232; 1873-376X; 1873-376X
• DOI: 10.1016/j.jchromb.2018.09.005

Most bioanalytical methods reported in literature for the quantitation of lapatinib in human plasma are either for lapatinib alone or lapatinib administered along with other tyrosine kinase inhibitors (TKIs) for therapeutic drug monitoring (TDM) in cancer patients. Recently there was a need for the quantitation of lapatinib in patients with end-stage renal disease (ESRD) receiving hemodialysis (HD). This special patient population normally receives many concomitant medications which have the potential to interfere with the quantitation of lapatinib. Here we describe an LC-MS-MS bioanalytical assay for the quantitation of lapatinib in human plasma containing potential concomitant medications which are commonly given to patients with ESRD receiving HD. The lapatinib calibration curve range was 2.50–1000 ng/mL. Lapatinib was fortified with its isotopically labeled internal standard in a 50 μL plasma aliquot and extracted with protein precipitation. The chromatographic separation was achieved on a Zorbax SB-C18 (5 μm, 2.1 × 50 mm) column with isocratic elution. Assay precision, accuracy, linearity, selectivity, sensitivity and analyte stability covering sample storage and analysis were established. No interferences were observed for the quantitation of lapatinib in the presence of concomitant medications. The validated LC-MS-MS method has been successfully applied to a clinical study for the determination of lapatinib concentrations in human plasma for patients with ESRD receiving HD. •No assays reported for lapatinib analysis for subjects with end-stage renal disease (ESRD) receiving hemodialysis (HD).•Subjects with ESRD receiving HD may be treated with medications that may interfere with the quantitation of lapatinib.•A LC-MS-MS assay has been validated and used to support a clinical study in subjects with ESRD receiving HD.