title: Confirmation of drug delivery after liver chemoembolization: direct tissue doxorubicin measurement by UHPLC-MS-MS.
abstract: Because liver cancer is rarely suitable for surgery, transcatheter arterial chemoembolization (TACE) is used for palliative therapy. In this procedure, an emulsion of doxorubicin in iodized oil is injected directly into liver tumors through a catheter positioned within the artery supplying blood flow to the tumor. At present, there is limited understanding of factors affecting the delivery and dispersion of doxorubicin within treated tumors during TACE. This study addresses the development and application of an ultrahigh-pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS-MS) method for rapid confirmation of drug delivery after TACE in a rabbit VX2 liver cancer model. Doxorubicin levels in liver tumors were measured using UHPLC-MS-MS and compared with computed tomography measured levels of iodized oil, a metric used clinically to indicate drug delivery. We found that tissue drug levels determined using UHPLC-MS-MS did not correlate with the regional iodized oil concentration (vehicle) within tumors following TACE, suggesting that chemotherapeutic drugs like doxorubicin spread throughout tumors, and that lack of iodized oil staining in portions of a tumor does not necessarily indicate inadequate therapy during TACE.
authors.affiliation: Department of Medicinal Chemistry and Pharmacognosy, University of Illinois College of Pharmacy, 833 S. Wood St, Chicago, IL 60612, USA.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Baumgarten
authors.forename: Ron C
authors.initials: RC
authors.lastname: Gaba
authors.forename: Richard B
authors.initials: RB
authors.lastname: van Breemen
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000032:analysis / Q000493:pharmacokinetics; D016461:Chemoembolization, Therapeutic / Q000295:instrumentation / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004317:Doxorubicin / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D004655:Emulsions / Q000737:chemistry; D004998:Ethiodized Oil / Q000493:pharmacokinetics; D008114:Liver Neoplasms, Experimental / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008297:Male; D011817:Rabbits; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014057:Tomography, X-Ray Computed
chemical_list: D000903:Antibiotics, Antineoplastic; D004655:Emulsions; D004998:Ethiodized Oil; D004317:Doxorubicin