Development of an ion mobility spectrometer for use in therapeutic monitoring of busulfan

• Grant number: 18/14957-9
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Start date: March 01, 2019
• End date: November 30, 2019
• Field of knowledge: Engineering - Biomedical Engineering - Medical Engineering
• Principal Investigator: Raphael Garcia Moreira
• Grantee: Raphael Garcia Moreira
• Company: Sonata Solutions Tecnologia Ltda
• CNAE: Atividades de serviços de complementação diagnóstica e terapêutica
• City: São Paulo
• Associated researchers: Eduardo Lorenzetti Pellini ; Samuel Katsuyuki Shinjo
• Associated scholarship(s): 19/06123-3 - Development of an ion mobility spectrometer for use in therapeutic monitoring of busulfan, BP.PIPE

Abstract

Therapeutic drug monitoring (TDM) consists of measuring medication concentrations in bodily fluids such as blood, plasma, serous fluid, saliva or urine. TDM's objective is to improve therapeutic selectivity, in other words, to reduce toxicity and promote therapeutic progress by means of administering the optimal dose to the patient. Busulfan (BU), combined with other drugs, is administered in the conditioning regimen of both allogeneic and autologous bone marrow transplantation (BMT), and in the conditioning regimen for treating rheumatoid arthritis through autologous transplantation of peripheral blood stem cells. The conventional method of quantification of BU and establish the optimal dose involves obtaining 7 to 12 plasma or saliva samples per dose of BU (by HPLC/ESI-MS/MS, high-performance liquid chromatography with electrospray ionization tandem mass spectrometry). This causes great inconvenience to both patients and staff, particularly to children. Mathematical models developed as a way of estimating the concentration of BU as a function of time are not robust enough, for example, if the dosages delay 15 minutes, the models are invalidated. In addition, few clinics and hospitals have the resources and people to run BU TDM locally in real time. The objective of this project will be the development of an IMS (ion mobility spectrometer), with electrospray ionization, ESI (electrospray ionization), ESI-IMS, dedicated to real-time TDM of the BU. As a methodology, the ESI-IMS device will be constructed from results obtained by fluidodynamic simulation and trajectory of the ions in the desolvation and drift regions. Tetrabutylammonium bromide (TBAB) and 2,6-Di-t-butylpyridine (2,6-DtBP) will be used as calibrators, finally the reduced mobility coefficient (K0BU) and collision cross section of the BU will be obtained. As a result, it is expected to detect BU (diluted solution) by means of the ESI-IMS, a fundamental step to deliver a complete and dedicated solution to BU's TDM for BMT cases. In 2017 the BMT numbers were: 2,388 in all Brazil and 903 in the State of São Paulo, according to the INCA (Instituto Nacional de Câncer) there are 70 centers prepared for BMT. SUS (Sistema Único de Saúde) performed 79% of BMT procedures while 21% were performed in private clinics. In this context, the accomplishment of the aforementioned objective represents a first embodiment aiming to deliver a dedicated TDM solution to the BU, in order to provide a more selective therapy to the patient, which represents benefits for the administrations of public and private health networks. (AU)