Certain drugs in urine, plasma, breast milk, and amniotic fluid have been quantitatively analyzed in the picogram to nanogram range by selective ion detection with two gas chromatograph—mass spectrometer—computer systems: an LKB 9000/PDP 12 operated in the electron impact mode and a Finnigan 1015/PDP 8/I operated in the chemical ionization mode. With the latter system, it is possible to monitor several drugs and drug metabolites and an internal standard in a single temperature-programmed analysis. Internal standards labeled with stable isotopes are preferred for selective ion detection. Diphenylhydantoin-2,4,5-13C has been used to quantify diphenylhydantoin, and pentobarbital-2,4(6) ,5-13C has been used to quantify amobarbital, secobarbital, caffeine, meperidine ("Demerol"), and phenobarbital in 50-200 µl samples of plasma and breast milk.
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Horning et al. (1973) studied this question.