Quantitative Characterization of Olaparib in Nanodelivery System and Target Cell Compartments by LC-MS/MS
Articolo
Data di Pubblicazione:
2019
Citazione:
Quantitative Characterization of Olaparib in Nanodelivery System and Target Cell Compartments by LC-MS/MS / R. Ottria, A. Ravelli, M. Miceli, S. Casati, M. Orioli, P. Ciuffreda. - In: MOLECULES. - ISSN 1420-3049. - 24:5(2019 Mar 01).
Abstract:
Olaparib, an orally active inhibitor of poly(ADP-ribose) polymerase(PARP), is the drug of choice in the treatment of gBRCA1/2+ metastatic breast cancers. Unfortunately, Olaparib is poorly soluble with low bioavailability and tumor accumulation; nano-delivery could be a good choice to overcome these disadvantages. Here, a rapid and robust HPLC-ESI-MS/MS method for the quantification of Olaparib in ferritin nano-carriers led to the development of cells compartments, different tissues, plasma and urines and were validated to assess the effects of nano-delivery on cell compartment distribution of the drug. This method allows the quantification of Olaparib within the linear range of 0.1-10ng/mL in cells culture medium and cell cytoplasm, of 0.5-10ng/mL in nuclei, of 0.5-100ng/mL in plasma and urine and of 10-500ng/mL in tissue samples (kidney and liver). The limit of quantification was found to be 1.54 ng/mL for liver, 2.87 ng/mL for kidney, and lower than 0.48 ng/mL for all matrices. The method has been applied to quantify Ola encapsulated in ferritin-nano-carriers during the nano-drug development. The application of the method to human BRCA-mutated cell model to quantify the Olaparib distribution after incubation of free or ferritin-encapsulated Olaparib is also reported. This sensitive method allows the quantification of low concentrations of Olaparib released from nano-carriers in different cell compartments, leading to the determination of the drug release and kinetic profile of an essential parameter to validate nano-carriers.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Olaparib; Olaparib nano-formulation; HPLC; bioanalysis; mass spectrometry; sample preparation
Elenco autori:
R. Ottria, A. Ravelli, M. Miceli, S. Casati, M. Orioli, P. Ciuffreda
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