The potential of F-19 NMR spectroscopy for rapid screening of cell cultures for models of mammalian drug metabolism

The use of microbial cultures as a complementary model for mammalian drug m etabolism has been well established previously. Here is a preliminary inves tigation into the potential of F-19 NMR spectroscopy as a rapid screening t ool to quantify the biotransformations of fluorine-containing model drugs. Biotransformations of three model drugs in 48 taxonomically diverse organis ms were measured by acquiring F-19 NMR spectra at 376 MHz. The presence of fluorine in the molecules allowed rapid, simultaneous detection of over 20 biotransformation products without sample pretreatment, chromatography, mas s spectrometric techniques or the use of radiolabelled substrates. The dete ction limit at 376 MHz using 5 mm NMR tubes was ca. 0.3 mug ml(-1) using a typical analysis time of 20 min per sample. With the recent advent of flow injection NMR technology, analysis time of 5 min could be achieved with les s sample. This approach may be used to develop fast small-scale microbial s creens for the biosynthesis of metabolite standards and production of novel drug analogues, whilst also having a role in reducing animal experiments n eeded to identify animal and human metabolites of fluorinated xenobiotics.