DRUG-METABOLISM STUDIES USING INTRINSIC AND EXTRINSIC LABELS A DEMONSTRATION USING N-15 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 (N-15) in a study of the metabolite pro file of a drug, in this case the benzodiazepine anesthetic agent midaz olam. We find equally high selectivity and comparable signal/noise cha racteristics for chlorine as for isotopic nitrogen demonstrating that the chlorine in midazolam is itself an effective label and that specia l synthesis to incorporate isotopic labels is not necessary. The power of either detection mode of CRIMS is shown by detecting 14 metabolite s, whereas only four had been previously determined. The ratios of N-1 5/Cl for each metabolite peak along with conventional mass spectra pro vide clues to the structures of these new metabolites.