A mixed-mode liquid chromatography-tandem mass spectrometric method for the determination of cytarabine in mouse plasma

A novel mixed-mode high performance liquid chromatographic system (HPLC) interfaced with an atmospheric pressure chemical ionization (APCI) source and a tandem mass spectrometer (MS/MS) was developed for the determination of cytarabine (ara-C) in mouse plasma to support pharmacodynamic studies. The mixed-mode reversed-phase ion-exchange chromatography column was adapted for sufficient retention and separation of a small and polar analyte. The impact of the mobile phase composition on both chromatographic separation and the ionization efficiency of the test compound in the positive mode was investigated. The potential of ionization suppression from endogenous biological matrices on the mixed-mode LC–APCI/MS/MS method was evaluated using the post-column infusion technique. Furthermore, the feasibility of using the mixed-mode HPLC–MS/MS method for the determination of the plasma concentrations of cytarabine in mice was demonstrated by comparing those obtained by the ion-pairing HPLC–MS/MS method.