title: PK and tissue distribution of docetaxel in rabbits after i.v. administration of liposomal and injectable formulations.
abstract: 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.
authors.affiliation: Research Laboratory of Medicinal chemistry and Biomaterials, Chongqing Pharmaceutical Engineering Research Center, School of Pharmacy, Chongqing Medical University, Chongqing, PR China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
authors.forename: Yu-Meng
authors.initials: YM
authors.lastname: Wei
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhong
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Bi-Bo
authors.initials: BB
authors.lastname: Li
authors.forename: Ya
authors.initials: Y
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Yu
mesh_terms: 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
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008081:Liposomes; D012996:Solutions; D043823:Taxoids; D000077143:Docetaxel