PK and tissue distribution of docetaxel in rabbits after i.v. administration of liposomal and injectable formulations.
A simple and sensitive HPLC method was established and validated for the determination of docetaxel (DTX) in rabbit plasma and tissue samples. Biosamples were spiked with paclitaxel as an internal standard and pre-treated by solid phase extraction (SPE). Sample separation was performed on a reverse-phase HPLC column at 30 degrees C by using a mobile phase of acetonitrile-methanol-0.02 M ammonium acetate buffer (pH 5.0) (20:47.5:32.5, v/v/v) at flow rate of 1.0 mL/min The UV absorbance of the samples was measured at the wavelength of 230 nm. The standard curves were linear over the ranges of 0.02525-2.525 microg/mL for plasma, 1.010-202.00 microg/g for lung, 0.202-20.20 microg/g for spleen, liver and kidney, 0.202-10.10 microg/g for heart and stomach, 0.0505-2.02 microg/g for brain, respectively. The limits of quantification (LOQ) were 10.0 ng/mL in the plasma samples and 20.0 ng/g in the tissue samples, respectively. The analysis method was successfully applied to pharmacokinetics and tissue distribution studies of DTX liposomes and DTX injection after i.v. administration to the rabbits. The results showed that the liposome carrier led to a significant difference in pharmacokinetics and tissue distribution profile compared to the conventional DTX injection.
Zhao
Ling
L
Research Laboratory of Medicinal chemistry and Biomaterials, Chongqing Pharmaceutical Engineering Research Center, School of Pharmacy, Chongqing Medical University, Chongqing, PR China.
Wei
Yu-Meng
YM
Zhong
Xiao-Dong
XD
Liang
Yan
Y
Zhang
Xue-Mei
XM
Li
Wei
W
Li
Bi-Bo
BB
Wang
Ya
Y
Yu
Yu
Y
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics*; D002138:Calibration; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D000077143:Docetaxel; D004337:Drug Carriers; D005615:Freezing; D007275:Injections, Intravenous; D008081:Liposomes; D011786:Quality Control; D011817:Rabbits; D012015:Reference Standards; D015203:Reproducibility of Results; D012996:Solutions; D013048:Specimen Handling; D013056:Spectrophotometry, Ultraviolet; D043823:Taxoids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008081:Liposomes; D012996:Solutions; D043823:Taxoids; D000077143:Docetaxel