Quantitation of paclitaxel in micro-sample rat plasma by a sensitive reversed-phase HPLC assay.
A sensitive high-performance liquid chromatographic (HPLC) method was developed for the determination of paclitaxel in micro-samples of rat plasma in order to study the mechanism of enhanced systemic exposure of paclitaxel co-administered with P-glycoprotein inhibitors. The assay involved solid-phase extraction procedures using 2'-methylpaclitaxel as the internal standard. Chromatographic separations were achieved using a ZORBAX ODS C18 column and mobile phase consisting of acetonitrile, methanol and ammonium acetate buffer (10 mM, pH 5.0) (48.5:16.5:35) pumped at 0.8 ml/min. The effluents were measured for UV absorption at 227 nm, with retention times of 8.5 and 11.0 min for paclitaxel and 2'-methylpaclitaxel, respectively. The chromatographic separation was excellent, with no endogenous interference. The standard curves showed a good linearity (r=0.9994) over the concentration ranges of 10-1,000 ng/ml. At 1,000 ng/ml, the absolute recoveries of paclitaxel and 2'-methylpaclitaxel are 89 and 90%, respectively. The intra- and inter-day variabilities of paclitaxel were both less than 15%. This validated method for the assay of paclitaxel in micro-sample rat plasma made it feasible to study the pharmacokinetics of the drug in a single rat.
Wang
L Z
LZ
Department of Pharmacy, National University of Singapore, Science Drive 4, S117543, Singapore.
Ho
P C
PC
Lee
H S
HS
Vaddi
H K
HK
Chan
Y W
YW
Yung
Chan Sui
CS
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D017239:Paclitaxel / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel