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

Abstract

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 oftheophylline in paired specimens of plasma and saliva from infants and children treated with theophylline for idiopathic apnea of prematurity, or for asthma, lSN-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) bek, veen results from the I",,vo different methods of analysis, which employed k, vo different mass spectrometers, the MAT 311 and HP 5989B, both in SIM mode. Good correlation was also observed bef,,veen plasma and saliva determinations (r = 0.97) and bel',,veen l',,vo methods of calculation, one using the regression curve and the other the least squares approach (r = 0.998). Applications to infants and children are clescribed.

A descriptive systematic review of salivary therapeutic drug monitoring in neonates and infants

“…The S/P ratio of 1.24 in Khanna et al's study [23] was similar to the observations of others [33,34], while Toback et al [29] suggest the ratio to be closer to 1. Also, that found by Culea et al [31] is low, although they found the ratio to be higher in the infants than children. The lower correlations with unstimulated saliva which were seen by Siegel et al [30] were thought to be due to greater variability in the theophylline saliva concentration due to changes in flow rates and pH.…”

“…Also, that found by Culea et al . is low, although they found the ratio to be higher in the infants than children. The lower correlations with unstimulated saliva which were seen by Siegel et al .…”

“…MS was used in the 2001 study by Culea et al . with 13 neonates whereas the enzyme multiplied immunoassay technique (EMIT) was used in the 1990 study by Siegel et al . with 31 children and HPLC by Toback et al .…”

“…Five studies were included in this review on TDM of theophylline in infants [23,[29][30][31][32]. Of these studies, four were deemed to have excellent correlation [29][30][31][32] (R = 0.97, P < 0.01). Of these four studies, two used stimulation to enhance saliva collection, one did not use stimulation and the other collected both stimulated and unstimulated saliva for comparison.…”

“…In the most recent study (2007) by Chereches-Panta et al [32], assessing 13 infants, gas chromatography-mass spectroscopy (MS) was used. MS was used in the 2001 study by Culea et al [31] with 13 neonates whereas the enzyme multiplied immunoassay technique (EMIT) was used in the 1990 study by Siegel et al [30] with 31 children and HPLC by Toback et al [29] in 1983 and Khanna et al in 1980 [23].…”