title: Simultaneous determination of nilotinib, imatinib and its main metabolite (CGP-74588) in human plasma by ultra-violet high performance liquid chromatography.
abstract: We describe a high performance liquid chromatography (HPLC) method that separates two of the currently licenced tyrosine kinase inhibitors (TKIs); nilotinib (AMN107, Tasigna) and imatinib (STI571, Glivec), together with its main metabolite, CGP-74588, from human plasma. After solid phase extraction the drug mix was separated through a Gemini C6-phenyl column (150 mm x 4.6mm, i.d.; 5 microm) (Phenomenex), UK) under isocratic mobile phase conditions of methanol:50mM ammonium acetate (pH 8) (65:35, v/v) with ultra-violet (UV) detection at 260 nm wavelength. For all compounds the intra-day coefficient of variation and bias were <3% and <5% respectively; and inter-day were <4% and <9%. This simple and novel method may be used to quantify levels of TKIs when used alone or in combination with drug treatments for clinical samples.
authors.affiliation: Department of Haematology, University of Liverpool, Liverpool, UK.
authors.forename: Andrea
authors.initials: A
authors.lastname: Davies
authors.forename: Alison K
authors.initials: AK
authors.lastname: Hayes
authors.forename: Katy
authors.initials: K
authors.lastname: Knight
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Watmough
authors.forename: Munir
authors.initials: M
authors.lastname: Pirmohamed
authors.forename: Richard E
authors.initials: RE
authors.lastname: Clark
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics; D001549:Benzamides; D001774:Blood Chemical Analysis / Q000379:methods* / Q000592:standards; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000592:standards; D002940:Circadian Rhythm / Q000502:physiology; D006801:Humans; D000068877:Imatinib Mesylate; D057230:Limit of Detection; D010879:Piperazines / Q000008:administration & dosage / Q000032:analysis* / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism / Q000493:pharmacokinetics; D010949:Plasma / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000032:analysis / Q000097:blood / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000008:administration & dosage / Q000032:analysis* / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism / Q000493:pharmacokinetics; D011786:Quality Control; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet / Q000379:methods / Q000592:standards
chemical_list: D001549:Benzamides; C464561:CGP 74588; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; C498826:nilotinib