ANALYSIS BY A COMBINATION OF GAS-CHROMATOGRAPHY AND TANDEM MASS-SPECTROMETRY - DEVELOPMENT OF QUANTITATIVE TANDEM-IN-TIME ION-TRAP MASS-SPECTROMETRY - ISOTOPE-DILUTION QUANTIFICATION OF 11-NOR-DELTA-9-TETRAHYDROCANNABINOL-9-CARBOXYLIC ACID

Collision-induced dissociation (CID) was performed in an ion-trap mass spectrometer to investigate quantification by isotope dilution and ga s chromatography coupled with tandem mass spectrometry (GC/MS/MS). The operating system software was modified to allow simutaneous CID of tw o ions differing only slightly in mass/charge ratios. Simultaneous exc itation of the base peaks of the parent compound and its deuterated an alog in a co-eluting GC peak leads to quantitative and reproducible fo rmation of daughter ions. Changing conditions in the mass analyzer as the GC peak elutes required broadening of the CID excitation frequency pattern. This had to be done so that relatively uniform dissociation energy would be imparted to both parent ions during the concentration changes associated with the elution of a GC peak. A commonly measured human metabolite of marijuana, 11-nor-delta-9-tetrahydrocannabinol-9-c arboxylic acid, was analyzed in freeze-dried urine. The mean value, 14 .0 +/- 0.61 (1 standard deviation) ng/mL, agrees very well with the GC /MS mean measured value of 14.1 +/- 0.45 ng/mL. The overall coefficien t of variation for the individual ion-trap MS/MS sample measurements i s 4.3%.