title: A new rapid and sensitive LC-MS assay for the determination of sorafenib in plasma: application to a patient undergoing hemodialysis.
abstract: A simple liquid chromatography-mass spectrometry method was developed and validated for quantification of sorafenib (Nexavar) in human plasma. After a solid-phase extraction procedure, the separation was performed within 2 minutes using an isocratic flow of a mobile phase consisting of formic acid/acetonitrile applied on a C18 analytical column. The analyte was detected by mass spectrometry in the single-ion monitoring mode. The method was validated according to the recommendations of the US Food and Drug Administration. The method was linear (r² > 0.99) between 10 and 10,000 ng/mL. The lower limits of detection and quantification were 5 and 10 ng/mL, respectively. Within-day and between-day imprecisions were less than 10.4%, and inaccuracy did not exceed 8.7%. The mean extraction recovery was 92.2%. The method also provided satisfactory results in terms of time stability and dilution integrity. Sorafenib plasma concentrations of the studied patient ranged between 1831 and 3459 ng/mL. This new technique is rapid, sensitive, and was applied to the determination of sorafenib plasma concentrations in a patient undergoing hemodialysis. Our results indicate that sorafenib is not cleared from plasma by hemodialysis, although analysis should be delayed after dialysis to avoid erratic fluctuations.
authors: Department of Oncology Biology, ICO René Gauducheau, Nantes Saint Herblain Cedex, France. christine.bobin-dubigeon@ico.unicancer.fr
authors: Christine
authors: C
authors: Bobin-Dubigeon
authors: Alexandra
authors: A
authors: Heurgue-Berlot
authors: Olivier
authors: O
authors: Bouché
authors: Marie-Bernadette
authors: MB
authors: Amiand
authors: Chantal
authors: C
authors: Le Guellec
authors: Jean-Marie
authors: JM
authors: Bard
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001557:Benzenesulfonates / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002138:Calibration; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000188:drug therapy; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D017809:Fatal Outcome; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications / Q000378:metabolism / Q000628:therapy; D057230:Limit of Detection; D008113:Liver Neoplasms / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011725:Pyridines / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D006435:Renal Dialysis; D015203:Reproducibility of Results; D052616:Solid Phase Extraction; D000077157:Sorafenib; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib