title: Determination of platinum drug release and liposome stability in human plasma by CE-ICP-MS.
abstract: An in vitro method for simultaneous assessment of platinum release and liposome stability of liposomal formulations in human plasma is demonstrated. The development and assessment of the method was performed on a PEGylated liposomal formulation containing cisplatin. Complete separation of free cisplatin, encapsulated cisplatin and cisplatin bound to plasma components was achieved by capillary electrophoresis (CE) separation and simultaneous monitoring of phosphorous (phospholipid) and platinum (cisplatin) by inductively coupled plasma mass spectrometry (ICP-MS). The method allows assessment of the encapsulation efficiency of the formulation, the physical stability of liposomes as well as cisplatin leakage in human plasma. The method was applied for studying the disintegration of liposomes and the interactions of leaked cisplatin with plasma components. Triggered release of the drug into plasma by sonication was also demonstrated. Analysis of liposomal formulations with alternative phospholipid compositions containing oxaliplatin showed similar results. Thus, the present in vitro method is suitable for mimicking the in vivo drug release profile in human plasma after administration of liposomal platinum formulations to patients. This approach may be of use in early drug development as well as in quality control.
authors.affiliation: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Tam T T N
authors.initials: TT
authors.lastname: Nguyen
authors.forename: Jesper
authors.initials: J
authors.lastname: Ostergaard
authors.forename: Stefan
authors.initials: S
authors.lastname: Stürup
authors.forename: Bente
authors.initials: B
authors.lastname: Gammelgaard
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood; D002945:Cisplatin / Q000008:administration & dosage / Q000097:blood*; D019075:Electrophoresis, Capillary / Q000379:methods*; D006801:Humans; D008081:Liposomes; D013058:Mass Spectrometry / Q000379:methods*; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000097:blood*; D000077150:Oxaliplatin; D010743:Phospholipids / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D009944:Organoplatinum Compounds; D010743:Phospholipids; D000077150:Oxaliplatin; D011092:Polyethylene Glycols; D002945:Cisplatin