title: Improved liquid chromatographic method for mitoxantrone quantification in mouse plasma and tissues to study the pharmacokinetics of a liposome entrapped mitoxantrone formulation.
abstract: A simple, rapid HPLC method for quantification of mitoxantrone in mouse plasma and tissue homogenates in the presence of a liposome entrapped mitoxantrone formulation (LEM-ETU) is described. Sample preparation is achieved by protein precipitation of 100 microl plasma or 200 microl tissue homogenate with an equal volume of methanol containing 0.5 M hydrochloric acid:acetonitrile (90:10, v/v). Ametantrone is used as the internal standard (i.s.). Mitoxantrone and i.s. are separated on a C18 reversed phase HPLC column, and quantified by their absorbance at 655 nm. In plasma, the standard curve is linear from 5 to 1000 ng/ml, and the precision (%CV) and accuracy (percentage of nominal concentration) are within 10%. In mouse tissue (heart, kidney, liver, lung, and spleen) homogenates (5%, w/v), the standard curve is linear from 25 to 2000 ng/ml, with acceptable precision and accuracy. The method was used to successfully quantify mitoxantrone in mouse plasma and tissue samples to support a pharmacokinetic study of LEM-ETU in mice.
authors.affiliation: Pharmacokinetics, Safety, and Efficacy Department, NeoPharm Inc., Research and Development, 1850 Lakeside Drive, 60085, Waukegan, IL, USA
authors.forename: Jenifer L
authors.initials: JL
authors.lastname: Johnson
authors.forename: Ateeq
authors.initials: A
authors.lastname: Ahmad
authors.forename: Sumsullah
authors.initials: S
authors.lastname: Khan
authors.forename: Yue-Fen
authors.initials: YF
authors.lastname: Wang
authors.forename: Aqel W
authors.initials: AW
authors.lastname: Abu-Qare
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Ayoub
authors.forename: Allen
authors.initials: A
authors.lastname: Zhang
authors.forename: Imran
authors.initials: I
authors.lastname: Ahmad
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D008081:Liposomes; D008297:Male; D051379:Mice; D008942:Mitoxantrone / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D008942:Mitoxantrone