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We describe a micro-scale method for determining serum theophylline. The chromatography system includes a muBondapack C18 column and acetonitrile, 70 ml/liter of sodium acetate buffer (10 mmol/liter, ph 4.0) as the mobile phase. Test serum or plasma, 30 mul, is mixed with an equal quantity of a solution containing the internal standard, beta-hydroxyethyltheophylline in acetonitrile/sodium acetate buffer (20 mmol/liter, pH 4.0), 7/43 by vol. After the precipitate is removed by centrifugation, the mixture is chromatographed and the amount of theophylline calculated from the ratio between peak heights for theophylline and the internal standard. Advantages include easy sample preparation, involving only addition of internal standard and centrifugation before injection, long column life, and the suitability of the internal standard, which is adjusted to a peak height equivalent to 20 mg of theophylline per liter for easy computation of results.

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\s=b\Simultaneous saliva and plasma theophylline levels in 12 chronic asthmatic children were measured by high pressure liquid chromatography following administration of a theophylline preparation. In five subjects, simultaneous plasma and salivary theophylline were measured one week later. A strongly positive correlation between plasma and salivary theophylline levels was found at all time periods tested.There was no substantial difference in the plasma-saliva theophylline ratio determined one week later. A predicted plasma Recent studies on drug therapy of ' patients with bronchial asthma have suggested the use of higher doses of theophylline than those previously recommended.1 In using such high doses, it is desirable to monitor the plasma concentration to indicate whether either therapeutic or potentially toxic levels have been reached.2 Pharmacokinetic studies in asthmatic patients show considerable variability in the plasma half-life of theophylline,3 with a range of 1.42 to 7.85 hours in children.4 Therefore, an appropriate dosage program for one patient may not be suitable for another. Determination of plasma levels at various time periods followFrom the Department of Pediatrics, University of California at Irvine. Reprints are not available.level was compared with the observed value. The proportionality of predicted to observed plasma theophylline levels using either the entire study group mean plasma-saliva ratio or each individual's ratio was approximately 1.00 with 9% variability. When a previously reported plasma-saliva theophylline ratio was used for comparison, the predicted plasma theophylline was 15% above the observed plasma level. (Am J Dis Child 131: [970][971][972] 1977) ing drug administration could estab¬ lish the high and low values and the rapidity of clearance (half-life) from the plasma. This would have great relevance in determining the proper dose. The obvious objection, particu¬ larly in the pediatrie age patient, is the discomfort and inconvenience of the multiple blood samples required. Koysooko et al5 found that a constant ratio existed between simul¬ taneously obtained plasma and saliva theophylline concentrations in normal adults. In a subsequent study involv¬ ing asthmatic children, these investi¬ gators were able to predict the plasma theophylline levels within 20% of the actual values by multiplying the mea¬ sured saliva theophylline level by the previously established plasma/saliva ratio." However, one recent report failed to confirm the consistency of this ratio.7 In the present study, we report the hourly variability of the plasma-saliva ratio, as well as the week-to-week consistency of the ratio, in the same patient. We also have compared the accuracy of predicting plasma theophylline levels using each individual's plasma-saliva ratio, the mean ratio of our entire group, and the mean ratio for the asthmatic patients reported in the literature." SUBJECTS AND METHODSTwelve asthmatic children (aged 6 to 14 years) were given 3.0 to 8.1 mg/kg of anhydrous theophylline every...