Development of a UPLC-ESI-MS/MS method for the determination of larotaxel in beagle dog plasma: application to the pharmacokinetic study.
A UPLC-ESI-MS/MS method has been developed and validated for the determination of larotaxel in beagle dog plasma. After addition of the internal standard, plasma samples were extracted by liquid-liquid extraction with methyl tert-butyl ether and separated on a 50×2.1 mm ACQUITY 1.7 μm C18 column (Waters, USA), with acetonitrile and 5 mM ammonium acetate as mobile phase, within a runtime of 3.0 min. The analytes were detected without interference in Multiple Reaction Monitoring mode with positive electrospray ionization. The linear range was 2.5-5,000 ng/mL. The intra-day and inter-day precisions (relative standard deviation, RSD, %) were within 9.3% and 10.2%, respectively, and the accuracy (relative error, RE, %) was less than 11.5%. The validated method was successfully applied to a pharmacokinetic study of larotaxel in beagle dogs after intravenous administration of larotaxel-loaded lipid microsphere with different doses of 0.4, 0.8, and 1.6 mg/kg. The area under the concentration-time curve and the peak concentration of larotaxel seemed to increase with increasing dose proportionally, suggesting linear pharmacokinetics.
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
Zhenzhen
Z
Liu
Bo
B
Zhang
Zhihong
Z
Liu
Song
S
Li
Guofei
G
Li
Lulu
L
Geng
Xu
X
Zhao
Kaishun
K
Bi
Xing
X
Tang
Xiaohui
X
Chen
D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood* / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods*; D004285:Dogs; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D043823:Taxoids / Q000097:blood* / Q000493:pharmacokinetics
D000970:Antineoplastic Agents; D043823:Taxoids; C531079:larotaxel