Liquid chromatography coupled to mass spectrometry (2015/03756-4)

Abstract

No drug treatment is completely free of risk and lack of response, adverse events and poor adherence may affect its effectiveness. There is also a large inter-individual variability in response to treatments with regard to efficacy and toxicity, and for many drugs, there is also a period of weeks to months to establish its efficacy. In this regard, this project aims to evaluate the importance of monitoring blood levels and salivary drug used in rheumatic autoimmune diseases in the monitoring of adherence to therapy. In addition, this project intends to use the monitoring of drug levels, based on pharmacokinetic studies and pharmacokinetics/pharmacodynamics modeling, to broaden the understanding of the possible cellular, tissue and immunological mechanisms involved in efficacy and adverse effects of these drugs with the prospect of reducing the damage and maintain therapeutic efficacy. The high-performance liquid chromatography (HPLC) coupled to mass spectrometry, which will be used to evaluate hydroxychloroquine, thalidomide and glucocorticoids levels, is considered the gold standard technology to qualitative and quantitative analysis of drugs in blood and its comparison with the dosage in the saliva is an improvement in simplification of the process. At present, there is no other methodology that matches the HPLC in relation to the analytical quality of the data obtained. This technique allows the quantification of multiple drugs in a single analysis, which helps to reduce the cost and time required to perform the analysis. The high sensitivity to detect the compounds at low concentrations and the specificity obtained allows precise determinations and elimination of interference generated by metabolites of the drugs and other endogenous and xenobiotic interferents. In the proposed project, there is a special need to obtain high accuracy and low imprecision due to the toxicity of the drugs studied and the need for precise adjustment of therapeutic levels. The implementation of this methodology dedicated to research in our center, with the necessary training of human resources, will enable the standardization and availability of this advanced technology to other muldisciplinary projects in various areas of science. (AU)