Capillary electrophoresis-electrospray mass spectrometry and HR-ICP-MS for the detection and quantification of B-10-boronophenylalanine (B-10-BPA) used in boron neutron capture therapy

摘要

Boron neutron capture therapy (BNCT) is a bimodal radiotherapeutic treatment based on the irradiation of neoplastic tissues with neutrons after the tissues have selectively accumulated molecules loaded with nuclides with large neutron capture cross-sections (such boron-10). Boron-10 carriers have been tested to a limited extent, and clinical trials have been conducted on sulfhydryl borane (B-10-BSH) and boronophenylalanine (B-10-BPA). However, precise and accurate measurements of boron-10 concentrations (0.1-100 mu g/g) in specimens and samples of limited size (mu g scale) are needed in order to be able to biologically characterise new compounds in predictive tissue dosimetry, toxicology and pharmacology studies as well as in clinical investigations. A new approach based on fast separation and detection of B-10-BPA performed by coupling capillary electrophoresis to electrospray mass spectrometry is reported. This method allows the quantitative analysis and characterisation of B-10-BPA in a short time with a high separation efficiency. Detection limits of 3 mu M for B-10-BPA and 30 ng/mL for B-10 were obtained with CE-ESI-MS. A quantification limit of 10 mu M for B-10-BPA (100 ng/mL for B-10) was attained. The total boron-10 concentration was determined by high-resolution inductively coupled mass spectrometry in order to validate the method. Boron-10 isotope measurements were carried out by HR-ICP-MS at medium resolution (R=4000) due to the presence of an isobaric interference at mass 10. Good agreement was obtained between the values from CE-ESI-MS and those from HR-ICP-MS. The method has been successfully used to determine the B-10-BPA in two lines of cultured cells.