Caffeine in saliva after peroral intake: early sample collection as a possible source of error

The influence of collection time on the correlation of caffeine concentrations in saliva and serum was examined in six healthy adults after peroral administration of 5 mg/kg caffeine citrate. Saliva was obtained from three different salivary glands (sublingual, right parotid, and left parotid) and evaluated separately. Caffeine concentrations in saliva and serum samples were determined by high-performance liquid chromatography. There were no differences in the caffeine concentrations in saliva from the three investigated glands (alpha = 0.05). Saliva samples collected earlier than 2 hours after caffeine intake showed higher caffeine concentrations than could be expected from the corresponding serum samples. Gingiva contamination was shown to be responsible for the higher caffeine concentrations in saliva, and it was concluded that saliva is a feasible matrix for therapeutic drug monitoring of caffeine. If caffeine is administered orally, saliva samples should be taken at least 2 hours after caffeine intake. If caffeine-containing beverages are used as the source of caffeine or if subjects do not cooperate by rinsing the mouth of caffeine contamination, an additional 60 minutes should be added before saliva sampling.