title: Quantification of Paclitaxel and Polyaspartate Paclitaxel Conjugate in Beagle Plasma: Application to a Pharmacokinetic Study.
abstract: An LC-MS/MS method for the determination of polyaspartate paclitaxel conjugate (PASP-PTX) and paclitaxel (PTX) in dog plasma with cephalomannine (Internal Standard for PASP-PTX, IS-I) and clopidogrel bisulfate (Internal Standard for PTX, IS-II) as the internal standards was developed and validated. Plasma samples of PASP-PTX were extracted by ethyl acetate following the hydrolysis reaction, while protein precipitation was used for the extraction of PTX using acetonitrile. Analytes were separated by a CAPCELL PAK C18 MG II column using a gradient elution with the mobile phase (A) 5 mM ammonium containing 0.1% formic acid, and (B) acetonitrile. Quantification was performed by monitoring the m/z transitions of 286.2/105.0 for PASP-PTX, 264.2/83.0 for IS-I, 854.4/286.0 for PTX, and 322.1/184.1 for IS-II in the ESI positive mode. This method was validated in terms of specificity, linearity, precision, accuracy, and stability. The lower limit of quantification was 0.15 µg/mL for PASP-PTX and 0.01 µg/mL for PTX, and the calibration curves were linear over 0.15-300 µg/mL for PASP-PTX and over 0.01-10 µg/mL for PTX. The samples were stable under all the tested conditions. The method was successfully applied to study the pharmacokinetic profiles of PASP-PTX and PTX in beagles following intravenous administration of PASP-PTX.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041 , China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Pathology, 324 Hospital of PLA, Chongqing 400020, China.
authors.forename: Junying
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041 , China.
authors.forename: Xiqian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041 , China.
authors.forename: Huiru
authors.initials: H
authors.lastname: Xie
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery System, West China School of Pharmacy, Sichuan University, Chengdu, Sichuan 610041 , China.
authors.forename: Yanran
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, the first affiliated hospital of Chongqing medical University, Chongqing 400016 , China.
authors.forename: Shuquan
authors.initials: S
authors.lastname: Guo
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D004285:Dogs; D005260:Female; D016014:Linear Models; D008297:Male; D017239:Paclitaxel / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D010455:Peptides / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D010455:Peptides; C017645:polyaspartate; D017239:Paclitaxel