Separation of liposome-entrapped mitoxantrone from nonliposomal mitoxantrone in plasma: pharmacokinetics in mice.

A method is described for quantification of the liposomal and nonliposomal forms of mitoxantrone (MTO) in mouse plasma after intravenous administration of liposome-entrapped MTO Easy-to-Use (LEM-ETU) formulation. This is based on the property of liposome-entrapped MTO (LEM) to pass through reversed-phase C(18) silica gel cartridges, while nonliposomal MTO or free MTO is retained with strong hydrophobicity and later is eluted with acidic methanol. Extraction of LEM and free MTO from plasma is performed in two steps. This technique is rapid and sensitive and can be used for a large series of sample preparation. The plasma samples are found stable after one freeze-thaw cycle. The recovery of MTO, as well as the precision, linearity, and accuracy of the method for both free and liposomal MTO, appears satisfactory for pharmacokinetic studies. The pharmacokinetic results in mice show a sustained release of MTO from LEM-ETU.