Pharmacokinetic study of two docetaxel preparations in Beagle dogs by a LC‐MS/MS method (1064.5)

Pharmacokinetic study of two docetaxel preparations in Beagle dogs by a LC‐MS/MS method Xin Huang, Guanlan Liu, Zhenzhou Jiang and Luyong Zhang Jiangsu Center for Drug Screening, China Pharmaceutical University, Nanjing 210009, China Objective: To establish a LC‐MS/MS method for determination of docetaxel in dog plasma and compare the PK profiles of two preparations in Beagle dogs. Methods: 12 dogs were divided into two groups and i.v. administrated test and reference preparations, respectively. Plasma samples were collected at different time points. The analytes were separated through a C 18 column with a mobile phase of methanol‐0.1% acetic acid water solution (85:15, v/v ), and analyzed by ESI in SRM mode. The ions were m/z 830.4→303.9 and 876.4→591.3 for docetaxel and paclitaxel(IS), respectively. The pharmacokinetic parameters were calculated by DAS 2.0 software. Results: The calibration curves were linear over the ranged 3‐2000 ng/mL ( r =0.9980) with the LLOQ 3 ng/mL. The within‐ and between‐batch precisions were within 8%, and the accuracy ranged from 94 to 110%. The overall recovery for docetaxel was about 91.3%. The main PK parameters t 1/2 , C max , MRT 0‐24 and AUC 0‐24 for test and reference preparations were: 7.3±2.0 h and 7.2±2.5 h, 796.1±321.8 ng/mL and 1248.0±178.6 ng/mL, 6.2±1.1 h and 5.3±0.8 h,948.4±100.2 ng·h/mL and 969.7±322.1 ng·h/mL. Conclusion: The method developed is sensitive, specific, rapid, and reproducible. It is suitable for PK studies of docetaxel in dogs. The results above shows no significant differences ( P >0.05) between the two preparation in PK parameters in dogs.