Validation of a high-performance liquid chromatographic ultraviolet detection method for the quantification of vandetanib in rat plasma and its application to pharmacokinetic studies.
OBJECTIVE
To develop a simple and sensitive high-performance liquid chromatography (HPLC) assay with ultraviolet detection method of vandetanib in rat plasma.


METHODS
Samples were extracted with methanol and acetonitrile, evaporated, and then the residue was reconstituted in mobile phase. Vandetanib and the internal standard (I.S.) trazodone hydrochloride were separated with gradient elution (on a C18 Atlantis column using a mobile phase of acetonitrile/0.5% triethylamine, pH 3.0, with a flow rate of 1.0 ml/min), then detected at 341 nm.


RESULTS
A linear curve over the concentration range of 80-4000 ng/ml (R² = 0.9998) was obtained. Intra- and inter-assay accuracy ranged from 98.80% to 103.08% and 95.32% to 98.40%, with high precision (R.S.D. % <5%), respectively. The mean absolute recovery was 96.65%.


CONCLUSIONS
A simple and sensitive HPLC assay with ultraviolet detection method was developed for the determination of vandetanib in rat plasma. This method is sufficient for pharmacokinetic studies of vandetanib in small animals and may be applied to human pharmacokinetic studies.
Hongjun
H
Lin
Dandan
D
Cui
Zhixing
Z
Cao
Qian
Q
Bu
Youzhi
Y
Xu
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
Yinglan
Y
Zhao
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D008297:Male; D010880:Piperidines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011799:Quinazolines / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000970:Antineoplastic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C452423:vandetanib