title: Simultaneous determination of gemcitabine and gemcitabine-squalene by liquid chromatography-tandem mass spectrometry in human plasma.
abstract: Gemcitabine-squalene is a new prodrug that self-organizes in water forming nanoassemblies. It exhibits better anti-cancer properties in vitro and in vivo than gemcitabine. A liquid chromatography/tandem mass spectrometry assay of gemcitabine-squalene and gemcitabine was developed in human plasma in order to quantitate gemcitabine and its squalene conjugate. After protein precipitation with acetonitrile/methanol (90/10, v/v), the compounds were analyzed by reversed-phase high performance liquid chromatography and detected by tandem mass spectrometry using multiple reaction monitoring. The method was linear over the concentration range of 10-10,000 ng/ml of human plasma for both compounds with an accuracy lower than 10.4% and a precision below 14.8%. The method showed a lower limit of quantitation of 10 ng/ml of human plasma for dFdC and dFdC-SQ. A preliminary in vivo study in mice was shown as application of the method as no significant difference between human and mice plasma for the analysis of dFdC and dFdC-SQ was demonstrated.
authors.affiliation: UPRES EA3535 Pharmacology and New Cancer Treatments, Institute Gustave Roussy - IFR54 and Paris XI University, 94800 Villejuif, France.
authors.forename: Hania
authors.initials: H
authors.lastname: Khoury
authors.forename: Alain
authors.initials: A
authors.lastname: Deroussent
authors.forename: L Harivardhan
authors.initials: LH
authors.lastname: Reddy
authors.forename: Patrick
authors.initials: P
authors.lastname: Couvreur
authors.forename: Gilles
authors.initials: G
authors.lastname: Vassal
authors.forename: Angelo
authors.initials: A
authors.lastname: Paci
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D015203:Reproducibility of Results; D013185:Squalene / Q000097:blood* / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D013185:Squalene; D000093542:Gemcitabine