TITLE:
Application of a Rapid ESI-MS/MS Method for Quantitative Analysis of Docetaxel in Polymeric Matrices of PLGA and PLGA-PEG Nanoparticles through Direct Injection to Mass Spectrometer
AUTHORS:
Pedram Rafiei, Deborah Michel, Azita Haddadi
KEYWORDS:
Docetaxel, EI-MS/MS, Direct Injection, Multiple Reaction Monitoring (MRM), Positive Electrospray Ionization (ESI+), PLGA, PLGA-PEG
JOURNAL NAME:
American Journal of Analytical Chemistry,
Vol.6 No.2,
January
20,
2015
ABSTRACT: Docetaxel is a member of taxan family of antineoplastic agents widely used in cancer chemotherapy. However, application of conventional chemotherapy with commercial formulation has been accompanied with matters of concern regarding drug’s biodistribution, pharmacokinetics, and pharmacodynamics. Polymeric nanoparticles have been widely used as unique drug delivery vehicles to circumvent such problems. Docetaxel-loaded poly (lactide-co-glycolide) (PLGA) and poly (lactide-co-glycolide)-poly (ethylene glycol) (PLGA-PEG) nanoparticles fit well in modifying drug’s pharmacokinetic characteristics as intravenous (IV) sustained-release delivery vehicles. In such circumstances, characterization of nanoparticles in terms of their drug-payload would be a necessary step. The majority of studies have used HPLC analysis method for docetaxel quantitation in polymeric nanoparticles. Herein, a rapid ESI-MS/MS method for quantitative analysis of docetaxel in polymeric matrices of PLGA and PLGA-PEG nanoparticles through direct injection to mass spectrometer has been developed and validated. The assay was validated over a range of 3.9 - 1000 ng/ml and 125 - 16,000 ng/ml. Samples were directly injected to the instrument through an isocratic elution (0.1% formic acid in methanol) and detection was performed on a Hybrid Triple Quadrupole/Linear Ion trap mass spectrometer with multiple reaction monitoring (MRM) mode via positive electrospray ionization (ESI) source. The run time and retention time were 2 and 0.6 minutes respectively. The method demonstrated acceptable level of accuracy and precision and was successfully applied for quantitative analysis of docetaxel in polymeric nanoparticles of PLGA and PLGA-PEG.