Determination of free and encapsulated oligonucleotides in liposome formulated drug product

Liposomes have been recognized as new delivery vehicles for peptide and oli gonucleotide drugs, offering effective drug protection and influencing drug distribution from the circulation to tissues. To ensure consistent formula tion behavior and drug distribution, the amounts of free and encapsulated a ctive pharmaceutical ingredient in the liposome formulation must be determi ned. A simple and reliable method has been developed for the determination of free and encapsulated oligonucleotide drugs in liposomes. Capillary elec trophoresis in entangled polyacrylamide solution was optimized for the anal ysis. Liposome samples were treated to release encapsulated oligonucleotide so that total concentration could be determined, and untreated liposomes w ere applied directly to capillary column to determine the fraction of free oligonucleotides. Recoveries are 96-105% and relative standard deviations a re generally 2-3%. Multiple liposome types were analyzed with satisfactory results. (C) 2000 Elsevier Science B.V. All rights reserved.