Analysis of neutral drugs in human plasma by fluoride attachment in liquid chromatography/negative ion electrospray tandem mass spectrometry

The analysis of several neutral drugs, mephenesin, guaifenesin, simvastatin, podophyllotoxin and inositol, was accomplished by negative ion electrospray ionization mass spectrometry (ESI‐MS) using adduct formation with three different halide ions. The fluoride, chloride and bromide adducts of the selected drugs exhibited intense signals in negative ion ESI. Under collision‐induced dissociation, the major product ions of bromide and chloride adducts were the nonspecific bromide and chloride anions, respectively. In contrast, fluoride adducts produced strong [MH]− ions as well as product ions with good intensity. Fluoride attachment liquid chromatography/negative ion electrospray tandem mass spectrometry (LC/ESI‐MS/MS) was applied to the analysis of the selected neutral drugs in human plasma. Detection limits in the range of 0.025–0.05 ng/mL were achieved using 0.5 mL plasma. Good linearity was observed for each of the drugs examined in human plasma over the range of 0.05–50 ng/mL. Copyright © 2004 John Wiley & Sons, Ltd.