Biophysical Society Thematic Meeting - November 16-20, 2015

Biophysics in the Understanding, Diagnosis, and Treatment of Infectious Diseases Poster Abstracts

38-POS Board 38 MALDI MSI and LCMS/MS as Tools for Gatifloxacin Distribution in Healthy Rat Brain Adeola Shobo , Tricia Naicker, Linda Bester, Sanil D. Singh, Glenn Maguire, Hendrik G. Kruger, Thavendran Govender. University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa. High mortality rates from tuberculosis (TB) remains a major concern worldwide. Besides the scourge of pulmonary TB, extra-pulmonary TB (EPTB) is increasing in developed as well as third-world countries. Tuberculosis meningitis (TBM) is the most common form of EPTB in human immunodeficiency syndrome (HIV) co-infected patients, and morbidity and mortality remains high in affected adults and children, despite the initiation of effective anti-TB therapy. This is possibly a consequence of reduced penetration of orally administered TB drugs in the CNS, resulting in treatment failure and drug resistance. The use of matrix-assisted laser desorption ionization-mass spectrometry imaging techniques as a suitable alternative for the localization of drug-tissue distribution for gatifloxacin will be able to answer questions regarding its distribution because other available methods require nuclear labeling and the detection of gamma rays produced by labeled compounds to localize the compound and hence causing a modification to the original structure of the active molecule. The aim of this study was to determine the brain distribution and the pharmacokinetic profile of gatifloxacin in healthy Sprague-dawley rats using matrix assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) and quantitative liquid chromatography tandem mass spectrometry (LCMS/MS). The MALDI MSI results showed the drug gradually diffused into the brain via the blood brain barrier and into the cortical regions of the rat brain reaching Cmax of 228.48 ng/ml at 120 min post-dose. As time elapses the drug slowly leaves the brain following the same path as it followed on its entry into the brain and finally concentrates at the frontal cortex. Thus we have shown that MALDI MSI is a valuable tool in the study of drug localization, which requires less complicated sample processing with better resolution for drug distribution studies.

61