Direct, simultaneous measurement of liposome-encapsulated and released drugs in plasma by on-line SPE-SPE-HPLC.
A method for the simultaneous measurement of liposome-encapsulated and released drugs in mouse plasma by on-line solid phase extraction (SPE)-SPE-HPLC with direct plasma injection was developed using a doxorubicin (DXR)-containing liposome formulation as the model drug. During SPE, the released DXR was extracted on the 1st restricted-access media (RAM) SPE column, whereas the liposomes were eluted. The eluted liposomes were collapsed on-line, and the released DXR was delivered to the 2nd RAM SPE column for extraction. The retained DXR on the SPE columns was analyzed via HPLC-fluorescent detector by switching the valves. The method was validated and applied to the pharmacokinetic study of DXR in mice after intravenous injection of DXR-containing liposomes.
DDS Research, Formulation Research Laboratories, Pharmaceutical Science & Technology, Eisai Co. Ltd., Tsukuba, Ibaraki, Japan. e-yamamoto@hhc.eisai.co.jp
Eiichi
E
Yamamoto
Kenji
K
Hyodo
Naozumi
N
Ohnishi
Takuya
T
Suzuki
Hiroshi
H
Ishihara
Hiroshi
H
Kikuchi
Naoki
N
Asakawa
D000085:Acetates; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004317:Doxorubicin / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D004355:Drug Stability; D004867:Equipment Design; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000097:blood* / Q000493:pharmacokinetics; D008297:Male; D000432:Methanol; D051379:Mice; D008807:Mice, Inbred BALB C; D015203:Reproducibility of Results; D052616:Solid Phase Extraction / Q000379:methods*
D000085:Acetates; D008081:Liposomes; D004317:Doxorubicin; C018824:ammonium acetate; D000432:Methanol