Quantitative Characterization of Olaparib in Nanodelivery System and Target Cell Compartments by LC-MS/MS
AbstractOlaparib, 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. View Full-Text
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Ottria, R.; Ravelli, A.; Miceli, M.; Casati, S.; Orioli, M.; Ciuffreda, P. Quantitative Characterization of Olaparib in Nanodelivery System and Target Cell Compartments by LC-MS/MS. Molecules 2019, 24, 989.
Ottria R, Ravelli A, Miceli M, Casati S, Orioli M, Ciuffreda P. Quantitative Characterization of Olaparib in Nanodelivery System and Target Cell Compartments by LC-MS/MS. Molecules. 2019; 24(5):989.Chicago/Turabian Style
Ottria, Roberta; Ravelli, Alessandro; Miceli, Matteo; Casati, Sara; Orioli, Marica; Ciuffreda, Pierangela. 2019. "Quantitative Characterization of Olaparib in Nanodelivery System and Target Cell Compartments by LC-MS/MS." Molecules 24, no. 5: 989.
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