Comparison of isotopic dilution methods for determination of theophylline in the plasma and saliva of infants and children

Isotope-dilution mass spectrometry (IDMS) using the direct inlet probe and an isotope dilution gas chromatographic-mass spectrometric (GC-IDMS) technique are presented for determination of theophylline in paired specimens of plasma and saliva from infants and children treated with theophylline for idiopathic apnea of prematurity, or for asthma. N-15-theophylline was used as internal standard. A non-invasive means of individualization of the dosage was achieved by analysis of levels of the drug in saliva secreted in response to stimulation with citric acid. There was good correlation (r = 0.99) between results from the two different methods of analysis, which employed two different mass spectrometers, the MAT 311 and HP 5989B, both in SIM mode. Good correlation was also observed between plasma and saliva determinations (r = 0.97) and between two methods of calculation, one using the regression curve and the other the least squares approach (r = 0.998). Applications to infants and children are described.