Analysis of 10B antitumoral compounds by means of flow-injection into ESI-MS/MS

Boron neutron capture therapy (BNCT) is a promising binary treatment for cancer. BNCT is based on the ability of the nonradioactive isotope (10)B to capture, with a very high probability, thermal neutrons. This nuclear reaction results in two particles (an alpha and a lithium nucleus). The particles have a high biological effectiveness, which is limited in tissue to approximately the diameter of one cell. If the reaction can be limited to a tumor cell, the physical characteristic opens up the possibility to selectively destroy cancer cells, while sparing the surrounding healthy tissue. Quality control of (10)B-containing compounds and their distribution at present are very important, and different analytical methods have been developed, such as time-of-flight secondary ion mass spectrometry (TOF-SIMS), electron energy loss spectrometry (EELS), prompt gamma analysis and inductively coupled plasma-optical emission spectrometry (ICP-OES). These methods allow the analyses of (10)B, but it is not possible to characterize the specific molecular compounds containing (10)B. For this reason, we propose a fast and quantitative method that permits the determination of closo-undecahydro-1-mercaptododecaborate (BSH) and (10)boron-phenylalanine (BPA) and their eventual metabolites. In particular, (10)B-containing compounds are detected by means of flow-injection electrospray tandem mass spectrometry (FI/ESI-MS/MS). This approach allows the identification of Boron compounds, BSH and BPA, using tandem mass spectrometry, and quantitative analysis is also possible (c.v. +/-4.7%; n = 5; linear range 10-10,000 ng/ml). Furthermore, (10)B-containing compounds were detected in actual biological sample (urine and plasma, diluted 10,000- and 1,000-fold, respectively) injecting a small volume (1 microl) of diluted samples.