Quantificação de farmacos em estudos de biodisponibilidade relativa por espectrometria de massas com a utilização da tecnica de fotoionização / Drug quantification for relative biovailability studies by means of photoionization mass spectrometry

AUTOR(ES)
DATA DE PUBLICAÇÃO

2006

RESUMO

The development of atmospheric pressure ionization techniques has been of utmost importance to turn high performance liquid chromatography coupled to mass spectrometry into a routine solution, enabling the development of robust, high performance, high sensitivity and specific quantitative methods. In this sense, the recent development of the atmospheric pressure photoionization technique is specially interesting, as it is making possible the ionization of a group active pharmacological entities hardly addressed by the traditional techniques, as is the case of steroid and other non polar compounds. However, especially in our region, there are only few organizations developing methods for drug quantification in pharmacokinetic studies by means of this technique. Within this setting, the present work aims at the development and evaluation of drug quantification methods for pharmacokinetic studies using photoionization, having anastrozole and dihydropyridine drugs as case studies. Tests performed have included, among others, the comparison of ionization methods and the evaluation of the influence of the dopant selected. Taking into account the evaluations and the acquired experience with the development of distinct analytical methods, it is believed this interface is capable to equally perform satisfactorily when applied to the evaluation of molecules handled by traditional ionization methods, as is the case of electrospray. For low proton affinity molecules, the use of anisole as dopant allowed to enhance the ionization efficiency by 10 to 100 fold. Acetone or anisol directly added to the mobile phase has also shown to be an interesting approach, as few apparatus are required, thus simplifying daily operations. This also assures a constant dopant flow rate as compared to the eluant flow rate, which is relevant to reduce variability on the ionization efficiency. It was also verified this approach does not damage the chromatographic column. Methods developed with this interface have shown to be sensitive, specific, precise and accurate, therefore meeting the requirements for bioanalytical method validation used for quantative determination of drugs in biological matrices. At last, by supporting the analysis of new compounds, as well as by increasing the sensitivity of bioanalytical methods due to a better ionization efficiency, this technique brings an important contribution to drug quantification and, in particular, to the performance of relative bioavailability studies

ASSUNTO(S)

biodisponibilidade espectrometria de massa medicamentos genericos - analise biological availability photoionization generic drugs fotoionização mass spectrometry

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