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

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.

Determination of total and unbound docetaxel in plasma by ultrafiltration and UPLC-MS/MS: application to pharmacokinetic studies

“…Depending on different experimental conditions, docetaxel and the IS may tend to generate different adducts when ionized through an ESI source. Although there are reports that exploited protonated adduct MRM transitions with good sensitivity 27 , in our studies, spectra revealed that docetaxel formed Na + adducts more easily than H + adducts even in the presence of formic acid. Under ESI + conditions respective precursor ions for docetaxel and the IS were [docetaxel + Na] + at m/z 830.0 and [paclitaxel + Na] + at m/z 876.2 as shown in Fig.…”

Identification of Modified and Unmodified Lipophilic B-Diketones Using Electrospray Ionisation Mass Spectrum (Esi-Ms)

“…In all these spectra, protonated species [M+H] + common in ESI(+)-MS were absent as it has been similarly reported [16] Although other researchers have confirmed predominant formation of protonated species in such studies [11,13]. Furthermore, Ramaroson-Raonizafinimanana [17] had also observed similar fragmentation of such lipophilic β-diketones as it was found in the mass spectrum of 2,4-diketone silyl ether derivatives described in Figure 6.…”

“…ESI-MS was also applied successfully for the qualitative analysis of green tea extract [12]. Quantitative analysis of docetaxel in polymeric matrices of poly (lactide-co-glycolide) and poly (lactide-co-glycolide)-poly (ethylene glycol) nanoparticles has been reported using ESI-MS [13]. It was observed that there was more intense formation of [M+H] + than [M+Na] + [13].…”

“…Quantitative analysis of docetaxel in polymeric matrices of poly (lactide-co-glycolide) and poly (lactide-co-glycolide)-poly (ethylene glycol) nanoparticles has been reported using ESI-MS [13]. It was observed that there was more intense formation of [M+H] + than [M+Na] + [13]. In as much as ESI-MS has become a global method for qualitative and quantitative analyses, there are no literature on the ESI-MS analyses of lipophilic β-diketones and there derivatives.…”

An Efficient Ambient Ionization Mass Spectrometric Approach to Detection and Quantification of the Mescaline Content of Commonly Abused Cacti from the Echinopsis Genus

“…gas, liquid or solid), an attribute which potentially offers numerous advantages. While other ambient techniques may perform similarly, including direct-injection electrospray ionization (DI-ESI) (19), easy ambient sonic-spray ionization (EASI) (20), and paper spray ionization (PSI) (21), DART-HRMS, which is enjoying increasing use as a sample screening tool for forensic labs, offers extremely fast analysis times and minimal methods development. The approach has been shown to work well for the rapid direct analysis of very complex matrices, including whole botanical samples such as leaves or seeds, extracts, and other plant products (22)(23)(24).…”