title: Liquid chromatography-tandem mass spectrometry for the determination of paclitaxel in rat plasma after intravenous administration of poly(L-glutamic acid)-alanine-paclitaxel conjugate.
abstract: A specific and sensitive liquid chromatography-tandem mass spectrometric method for quantitative determination of paclitaxel in rat plasma was developed and validated using docetaxel as an internal standard. Liquid-liquid extraction using tert-butyl methyl ether was used to extract the drug and the internal standard from plasma. The separation of paclitaxel was performed on a C(18) column with a mobile phase of acetonitrile:water:formic acid (65:35:0.1, v/v/v) over 5min. The assay was based on the selected reaction monitoring transitions at m/z of the precursor-product ion transitions m/z 854.2-->286.1 for paclitaxel and 808.3-->527.2 for internal standard. The lower limit of quantification was 0.5ng/mL based on 100microL of plasma. Intra- and inter-day assay variations were less than 15%, and the accuracy values were between 95.4 and 105.4%. The extraction recoveries ranged from 96.7 to 103.7% across the calibration curve range. The method was successfully applied to measurement of low concentrations of paclitaxel or regenerated paclitaxel in plasma after intravenous administration of a single dose (10mg/kg) of a poly(l-glutamic acid)-alanine-paclitaxel conjugate to rats.
authors.affiliation: Key Laboratory of Drug Metabolism and Pharmacokinetics, Beijing Institute of Pharmacology and Toxicology, 27 Taiping Road, Beijing 100850, China. zhangshq@hotmail.com
authors.forename: Shuang-Qing
authors.initials: SQ
authors.lastname: Zhang
authors.forename: Yi-Ning
authors.initials: YN
authors.lastname: Song
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: He
authors.forename: Bo-Hua
authors.initials: BH
authors.lastname: Zhong
authors.forename: Zhen-Qing
authors.initials: ZQ
authors.lastname: Zhang
mesh_terms: D000409:Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood* / Q000493:pharmacokinetics; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D002853:Chromatography, Liquid / Q000592:standards; D004355:Drug Stability; D007275:Injections, Intravenous; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D011099:Polyglutamic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000592:standards
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011099:Polyglutamic Acid; D000409:Alanine; D017239:Paclitaxel; C509139:paclitaxel poliglumex