Quantification of Paclitaxel and Polyaspartate Paclitaxel Conjugate in Beagle Plasma: Application to a Pharmacokinetic Study

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....

Full description

Saved in:
Bibliographic Details
Published in:Journal of chromatographic science 2017-03, Vol.55 (3), p.222-231
Main Authors: Gao, Yangyang, Chen, Junying, Zhang, Xiqian, Xie, Huiru, Wang, Yanran, Guo, Shuquan
Format: Article
Language:English
Subjects:
Animals
Chromatography, Liquid - methods
Dogs
Female
Linear Models
Male
Paclitaxel - blood
Paclitaxel - chemistry
Paclitaxel - pharmacokinetics
Peptides - blood
Peptides - chemistry
Peptides - pharmacokinetics
Reproducibility of Results
Sensitivity and Specificity
Tandem Mass Spectrometry - methods
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0021-9665
1945-239X
DOI:10.1093/chromsci/bmw174