Development and validation of a LC/TOF MS method for the determination of carboplatin and paclitaxel in nanovesicles

Johnson Mo, Paul Eggers, C.L. Raston, Lee Yong Lim

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Abstract

Carboplatin and paclitaxel co-loaded nanovesicles (CPT-PTX-CLV), a novel intravenous formulation void of cremophor EL, may have significant advantages over conventional carboplatin and paclitaxel formulations with respect to tumor targeting, sustained drug release, reduced toxicity, and synergistic efficacy profiles. The aim of this study was to develop and validate a rapid, specific, sensitive, and reliable liquid chromatography-time of flight-mass spectrometry (LC/TOF MS)-based bioanalytical method for the simultaneous quantification of CPT and PTX in a fetal bovine serum (FBS) vehicle containing the dispersed nanovesicles. The analytes were extracted from FBS by simple protein precipitation, with subsequent separation of CPT and PTX on a Waters HPLC SunFire C18 column at a flow rate of 0.25 ml/min using gradient elution mode. The total analytical time was only 12 min. Detection and quantitation was performed by electrospray ionization (ESI) in the positive ionization mode with selective ion monitoring (SIM) at m/z 310.0152 for CPT and 876.3224 for PTX. The calibration curves were linear over the concentration range of 10-4,000 ng/ml for CPT and 5-2,000 ng/ml for PTX (r 2 > 0.99), with the respective lower limit of quantification (LLOQ) at 10 and 5 ng/ml. The intra- and inter-day precision and accuracy of analysis of the quality control samples at low, medium, and high concentration levels were ≤13.6 % relative standard deviation (RSD) and ≤;14.6 % relative errors (RE). The rapid, sensitive, and reproducible LC/TOF MS method may be used to support preclinical and clinical pharmacological studies of the CPT-PTX-CLV administered by injection in animal and human cancer models. [Figure not available: see fulltext.] © 2014 Springer-Verlag Berlin Heidelberg.
Original languageEnglish
Pages (from-to)2659-2667
JournalAnalytical and Bioanalytical Chemistry
Volume406
Issue number11
Early online date27 Feb 2014
DOIs
Publication statusPublished - Apr 2014

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