title: Extraction protocol and mass spectrometry method for quantification of doxorubicin released locally from prodrugs in tumor tissue.
abstract: The localized conversion of inactive doxorubicin prodrug chemotherapeutics to pharmacalogically active forms is difficult to quantify in mouse tumor models because it occurs only in small regions of tissue. The tumor tissue extraction protocol and LC-MS/MS analysis method described here were optimized to obtain a detection limit of 7.8 pg for the activated doxorubicin and 0.36 ng for the doxorubicin prodrug. This method can be useful for determining the biodistribution and activation efficiency for many different doxorubicin prodrugs. It can also be used for quantification of doxorubicin from tumor models that have poor vascularization resulting in low tissue accumulation.
authors.affiliation: Department of Bioengineering, Moores Cancer Center, University of California San Diego, 3855 Health Sciences Dr. # 0815, La Jolla, CA 92093-0815, USA. sibsen@ucsd.edu
authors.forename: Stuart
authors.initials: S
authors.lastname: Ibsen
authors.forename: Yongxuan
authors.initials: Y
authors.lastname: Su
authors.forename: John
authors.initials: J
authors.lastname: Norton
authors.forename: Eran
authors.initials: E
authors.lastname: Zahavy
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hayashi
authors.forename: Stephen
authors.initials: S
authors.lastname: Adams
authors.forename: Wolf
authors.initials: W
authors.lastname: Wrasidlo
authors.forename: Sadik
authors.initials: S
authors.lastname: Esener
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004317:Doxorubicin / Q000032:analysis* / Q000302:isolation & purification / Q000493:pharmacokinetics*; D015251:Epirubicin / Q000032:analysis; D005260:Female; D057230:Limit of Detection; D016014:Linear Models; D008175:Lung Neoplasms / Q000737:chemistry / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D011355:Prodrugs / Q000032:analysis* / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D011355:Prodrugs; D015251:Epirubicin; D004317:Doxorubicin
keywords: LC-MS/MS; doxorubicin; prodrug; tissue extraction