Quantitative Characterization of Olaparib in Nanodelivery System and Target Cell Compartments by LC-MS/MS

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 5; p. 989
• Main Authors: Ottria, Roberta, Ravelli, Alessandro, Miceli, Matteo, Casati, Sara, Orioli, Marica, Ciuffreda, Pierangela
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 11.03.2019; MDPI
• Subjects: Accuracy; bioanalysis; Bioavailability; Breast cancer; Calibration; Cancer; Cell culture; Clinical trials; Compartments; Cytoplasm; DNA repair; Drug delivery systems; Drug development; Encapsulation; Ferritin; High-performance liquid chromatography; HPLC; Kidneys; Liquid chromatography; Liver; Low concentrations; mass spectrometry; Metastases; Nanoparticles; Olaparib; Olaparib nano-formulation; Plasma; Poly(ADP-ribose) polymerase; Ribose; sample preparation; Urine; Olaparib nano-formulation; mass spectrometry; Olaparib; bioanalysis; HPLC; sample preparation
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24050989

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.