Determination of doxorubicin in rabbit ocular tissues and pharmacokinetics after intravitreal injection of a single dose of doxorubicin-loaded poly-beta-hydroxybutyrate microspheres.
A validated HPLC method was developed for the quantification of doxorubicin in rabbit ocular tissues using solid phase extraction and ultraviolet detection. Chromatographic separation of doxorubicin in various ocular tissues was performed on a C18 column. The mobile phase was composed of 0.2 M KH2PO4 buffer solution, acetonitrile and triethylamine in volumetric ratio of 70/30/0.2, adjusted to pH 4.0 with orthophosphoric acid. The calibration curve was linear over the range of 0.03-10, 0.03-10, 0.05-10 and 0.05-10 microg/ml in vitreous body, iris, retina/choroids and sclera, respectively. The intra-day and inter-day precisions in all ocular tissues were smaller than 4.95% and 5.73%, and the accuracies were about 100%. The extraction recoveries of doxorubicin in all of the ocular tissues were between 83.47% and 96.33%. After intravitreal administration of doxorubicin-loaded poly-beta-hydroxybutyrate microspheres, doxorubicin level in ocular tissues was much lower than that for administration of free doxorubicin, which was helpful to reduce the associated toxicity to surrounding tissues. Doxorubicin was detectable even after tens of days in the studied ocular tissues.
Hu
Tao
T
School of Pharmacy, Fudan University, Shanghai 200032, China.
Le
Qihua
Q
Wu
Zhiyi
Z
Wu
Wei
W
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000032:analysis* / Q000493:pharmacokinetics*; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000032:analysis* / Q000493:pharmacokinetics*; D005123:Eye / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D006885:Hydroxybutyrates; D007202:Indicators and Reagents; D008845:Microinjections; D008863:Microspheres; D011091:Polyesters; D011817:Rabbits; D012015:Reference Standards; D015203:Reproducibility of Results; D014822:Vitreous Body; D000094122:Polyhydroxybutyrates
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D006885:Hydroxybutyrates; D007202:Indicators and Reagents; D011091:Polyesters; C003182:poly-beta-hydroxybutyrate; D000094122:Polyhydroxybutyrates