Drug metabolism studies using "intrinsic" and "extrinsic" labels. A demonstration using 15N vs. Cl in midazolam.

The chemical reaction interface for mass spectrometry (CRIMS) has been used to evaluate the ability of an "intrinsic" label (chlorine) to replace an "extrinsic" label (15N) in a study of the metabolite profile of a drug, in this case the benzodiazepine anesthetic agent midazolam. We find equally high selectivity and comparable signal/noise characteristics for chlorine as for isotopic nitrogen demonstrating that the chlorine in midazolam is itself an effective label and that special synthesis to incorporate isotopic labels is not necessary. The power of either detection mode of CRIMS is shown by detecting 14 metabolites, whereas only four had been previously determined. The ratios of 15N/Cl for each metabolite peak along with conventional mass spectra provide clues to the structures of these new metabolites.